m6A Regulator Information

General Information of the m6A Regulator (ID: REG00007)

Regulator Name	Methyltransferase-like 3 (METTL3)
Synonyms	N6-adenosine-methyltransferase catalytic subunit; hMETTL3; N6-adenosine-methyltransferase 70 kDa subunit; MT-A70; MTA70 Click to Show/Hide
Gene Name	METTL3
Sequence	MSDTWSSIQAHKKQLDSLRERLQRRRKQDSGHLDLRNPEAALSPTFRSDSPVPTAPTSGG PKPSTASAVPELATDPELEKKLLHHLSDLALTLPTDAVSICLAISTPDAPATQDGVESLL QKFAAQELIEVKRGLLQDDAHPTLVTYADHSKLSAMMGAVAEKKGPGEVAGTVTGQKRRA EQDSTTVAAFASSLVSGLNSSASEPAKEPAKKSRKHAASDVDLEIESLLNQQSTKEQQSK KVSQEILELLNTTTAKEQSIVEKFRSRGRAQVQEFCDYGTKEECMKASDADRPCRKLHFR RIINKHTDESLGDCSFLNTCFHMDTCKYVHYEIDACMDSEAPGSKDHTPSQELALTQSVG GDSSADRLFPPQWICCDIRYLDVSILGKFAVVMADPPWDIHMELPYGTLTDDEMRRLNIP VLQDDGFLFLWVTGRAMELGRECLNLWGYERVDEIIWVKTNQLQRIIRTGRTGHWLNHGK EHCLVGVKGNPQGFNQGLDCDVIVAEVRSTSHKPDEIYGMIERLSPGTRKIELFGRPHNV QPNWITLGNQLDGIHLLDPDVVARFKQRYPDGIISKPKNL Click to Show/Hide
Family	MT-A70-like family
Function	The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some RNAs and regulates various processes such as the circadian clock, differentiation of embryonic and hematopoietic stem cells, cortical neurogenesis, response to DNA damage, differentiation of T-cells and primary miRNA processing. In the heterodimer formed with METTL14, METTL3 constitutes the catalytic core. N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability, processing, translation efficiency and editing. In embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization, promoting differentiation of ESCs. Involved in the response to DNA damage: in response to ultraviolet irradiation, METTL3 rapidly catalyzes the formation of m6A on poly(A) transcripts at DNA damage sites, leading to the recruitment of POLK to DNA damage sites. M6A is also required for T-cell homeostasis and differentiation: m6A methylation of transcripts of SOCS family members (SOCS1, SOCS3 and CISH) in naive T-cells promotes mRNA destabilization and degradation, promoting T-cell differentiation. Inhibits the type I interferon response by mediating m6A methylation of IFNB. Mediates m6A methylation of Xist RNA, thereby participating in random X inactivation: m6A methylation of Xist leads to target YTHDC1 reader on Xist and promote transcription repression activity of Xist. M6A also regulates cortical neurogenesis. METTL3 mediates methylation of pri-miRNAs, marking them for recognition and processing by DGCR8. Acts as a positive regulator of mRNA translation independently of the methyltransferase activity. Its overexpression in a number of cancer cells suggests that it may participate in cancer cell proliferation by promoting mRNA translation. Click to Show/Hide
Gene ID	56339
Uniprot ID	MTA70_HUMAN
Regulator Type	WRITER ERASER READER
Mechanism Diagram	Click to View the Original Diagram

Target Genes	Click to View Potential Target Genes of This Regulator

Full List of Target Gene(s) of This m6A Regulator and Corresponding Disease/Drug Response(s)

METTL3 can regulate the m6A methylation of following target genes, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulted from the regulation of certain target gene.

Browse Target Gene related Disease

Browse Target Gene related Drug

72 kDa type IV collagenase (MMP2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 7.46E-01 p-value: 1.39E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.08E+00	GSE60213

Melanoma [ICD-11: 2C30]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[1]
Responsed Disease	Melanoma [ICD-11: 2C30]
Target Regulation	Up regulation
Cell Process	Cell invasion/migration
In-vitro Model	451Lu	Cutaneous melanoma	Homo sapiens	CVCL_6357
	A-375	Amelanotic melanoma	Homo sapiens	CVCL_0132
	A375-MA2	Amelanotic melanoma	Homo sapiens	CVCL_X495
	MeWo	Cutaneous melanoma	Homo sapiens	CVCL_0445
	SK-MEL-2	Melanoma	Homo sapiens	CVCL_0069
	WM164	Cutaneous melanoma	Homo sapiens	CVCL_7928
	WM3211	Acral lentiginous melanoma	Homo sapiens	CVCL_6797
	WM3918	Melanoma	Homo sapiens	CVCL_C279
	WM793	Melanoma	Homo sapiens	CVCL_8787
Response Summary	METTL3 is upregulated in human melanoma and plays a role in invasion/migration through MMP2. METTL3 overexpression promotes accumulation of 72 kDa type IV collagenase (MMP2) and N-cadherin in melanoma cells.

Abnormal spindle-like microcephaly-associated protein (ASPM)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Mouse testis	Mus musculus
Treatment: Mettl3 knockout mouse testis Control: Mouse testis		GSE99771
Regulation		logFC: -3.99E+00 p-value: 5.74E-06
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.27E+00	GSE60213

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[2]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Cell Process	Cells growth
	Cell metastasis
In-vitro Model	SNU-449	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0454
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	Hepg3b (Hepg3b were purchased from the American Type Culture Collection (ATCC, USA))
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
Response Summary	The N6-methyladenosine (m6A) modification of ASPM mRNA mediated by METTL3 promoted its expression in liver hepatocellular carcinoma.

Adenomatous polyposis coli protein (APC)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 6.65E-01 p-value: 8.92E-49
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.14E+00	GSE60213

Esophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[3]
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
	Cell cycle			hsa04110
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glycolysis
In-vitro Model	TE-10	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1760
	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
	KYSE-70	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1356
	KYSE-450	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1353
	KYSE-410	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1352
	KYSE-30	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1351
	KYSE-180	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1349
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
	KYSE-140	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1347
	HET-1A	Normal	Homo sapiens	CVCL_3702
In-vivo Model	For the subcutaneous implantation model, 1 × 10⁶ cells were injected subcutaneously into the flank regions of female BALB/c nude mice (4-5 weeks).
Response Summary	m6A-RNA immunoprecipitation sequencing revealed that METTL3 upregulates the m6A modification of Adenomatous polyposis coli protein (APC), which recruits YTHDF for APC mRNA degradation. Our findings reveal a mechanism by which the Wnt/Bete-catenin pathway is upregulated in ESCC via METTL3/YTHDF-coupled epitranscriptomal downregulation of APC.

AF4/FMR2 family member 4 (AFF4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -6.53E-01 p-value: 1.79E-17
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.64E+00	GSE60213

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[4]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Up regulation
Cell Process	Glucose metabolism
Response Summary	AF4/FMR2 family member 4 (AFF4), two key regulators of NF-Kappa-B pathway (IKBKB and RELA) and MYC were further identified as direct targets of METTL3-mediated m6A modification.overexpression of METTL3 significantly promoted Bladder cancer cell growth and invasion.

Angiopoietin-1 receptor (TEK)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 3.39E+00 p-value: 6.45E-138
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 3.75E+00	GSE60213

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[6]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Up regulation
Cell Process	Cellular proliferation and survival
In-vitro Model	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
In-vitro Model	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
In-vivo Model	For induction of BCa, 6-8-week-old mice were treated with drinking water containing 500 ug/ml BBN for 16 weeks and then given normal water for another 10 weeks. Tamoxifen was intraperitonelly injected to the mice with 0.08 mg/g of body weight each day for 3 days in order to inductively knock out the target gene.
Response Summary	Deletion of Mettl3 leads to the suppression of Angiopoietin-1 receptor (TEK) and VEGF-A,ablation of Mettl3 in bladder urothelial attenuates the oncogenesis and tumor angiogenesis of bladder cancer.

Apoptosis regulator BAX (BAX)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Embryonic stem cells	Mus musculus
Treatment: METTL3 knockout mESCs Control: Wild type mESCs		GSE156481
Regulation		logFC: -5.89E-01 p-value: 1.41E-07
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.02E+01	GSE60213

Enterovirus [ICD-11: 1A2Y]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[7]
Responsed Disease	Enterovirus [ICD-11: 1A2Y]
Target Regulation	Up regulation
Pathway Response	Autophagy	hsa04140
	Apoptosis	hsa04210
Cell Process	Cell proliferation and metastasis
	Cell apoptosis
	Cell autophagy
In-vitro Model	Schwann cells (A type of glial cell that surrounds neurons)
Response Summary	Knocking down METTL3 prevented Enterovirus 71-induced cell death and suppressed Enterovirus 71-induced expression of Apoptosis regulator BAX (BAX) while rescuing Bcl-2 expression after Enterovirus 71 infection. Knocking down METTL3 inhibited Enterovirus 71-induced expression of Atg5, Atg7 and LC3 II. Knocking down METTL3 inhibited Enterovirus 71-induced apoptosis and autophagy.

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation
Pathway Response	Apoptosis			hsa04210
	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
Response Summary	Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Apoptosis regulator BAX (BAX) and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and Cyclin D1.

Apoptosis regulator Bcl-2 (BCL2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Th1 cell line	Mus musculus
Treatment: METTL3 knockout splenic Th1 cells Control: Wild type splenic Th1 cells		GSE129648
Regulation		logFC: 7.38E-01 p-value: 3.55E-06
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 6.70E+00	GSE60213

Enterovirus [ICD-11: 1A2Y]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[7]
Responsed Disease	Enterovirus [ICD-11: 1A2Y]
Target Regulation	Down regulation
Pathway Response	Autophagy	hsa04140
	Apoptosis	hsa04210
Cell Process	Cell proliferation and metastasis
	Cell apoptosis
	Cell autophagy
In-vitro Model	Schwann cells (A type of glial cell that surrounds neurons)
Response Summary	Knocking down METTL3 prevented Enterovirus 71-induced cell death and suppressed Enterovirus 71-induced expression of BAX while rescuing Apoptosis regulator Bcl-2 (BCL2) expression after Enterovirus 71 infection. Knocking down METTL3 inhibited Enterovirus 71-induced expression of Atg5, Atg7 and LC3 II. Knocking down METTL3 inhibited Enterovirus 71-induced apoptosis and autophagy.

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[9]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Up regulation
Pathway Response	Apoptosis	hsa04210
Cell Process	Cell differentiation and apoptosis
In-vitro Model	HSPC (Human hematopoietic stem cell)
In-vivo Model	500,000 selected cells were injected via tail vein or retro-orbital route into female NSG (6-8 week old) recipient mice that had been sublethally irradiated with 475 cGy one day before transplantation.
Response Summary	METTL3 depletion in human myeloid leukemia cell lines induces cell differentiation and apoptosis and delays leukemia progression in recipient mice in vivo. Single-nucleotide-resolution mapping of m6A coupled with ribosome profiling reveals that m6A promotes the translation of c-MYC, Apoptosis regulator Bcl-2 (BCL2) and PTEN mRNAs in the human acute myeloid leukemia MOLM-13 cell line. Moreover, loss of METTL3 leads to increased levels of phosphorylated AKT.

B-cell lymphomas [ICD-11: 2A86]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[10]
Responsed Disease	B-cell lymphomas [ICD-11: 2A86]
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
	Autophagy			hsa04140
Cell Process	Cell proliferation and metastasis
	Cell apoptosis
In-vitro Model	ATDC-5	Mouse teratocarcinoma	Mus musculus	CVCL_3894
In-vivo Model	For MIA + SAH control, S-adenosylhomocysteine (SAH), Mettl3 inhibitor (10 mg/kg) (MCE, NJ, USA) was injected intraperitoneally before MIA injection and maintained twice a week until mice were sacrificed.
Response Summary	Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) induced temporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by TNF-alpha stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Apoptosis regulator Bcl-2 (BCL2) signal axis which provides promising therapeutic strategy for temporomandibular joint osteoarthritis.

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
Response Summary	Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Apoptosis regulator Bcl-2 (BCL2) and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and Cyclin D1.

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[11]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	The mice were housed with filtered air, 12 h light/dark cycle, constant temperature (25℃), relative humidity (50±5%) and free access to food and water. In order to establish a human NSCLC xenograft model, 5×10⁶ H1299, sh-METTL3-H1299 and METTL3 stably overexpressed H1299 cells (2×10⁶ per mouse) were subcutaneously injected into mice. Tumor growth was observed daily. Tumor volume was calculated as follows: 0.5× (length × width²). At 24 days post-inoculation, the maximum diameter exhibited by a single subcutaneous tumor was 15 mm and mice were anesthetized by intraperitoneal administration of sodium pentobarbital (50 mg/kg), then sacrificed by cervical dislocation.
Response Summary	METTL3 regulated cellular growth, survival and migration in non-small cell lung cancer. METTL3 promoted non-small cell lung cancer progression by modulating the level of Apoptosis regulator Bcl-2 (BCL2).

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	MCF-10A	Normal	Homo sapiens	CVCL_0598
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
In-vivo Model	Mice were maintained at 22 ± 2 ℃ with a humidity of 35 ± 5% under a 12 h light and 12 h dark cycle, with free access to water and food. For the HFD experiment, female control (Fto^flox/flox) and adipose-selective fto knockout (Fabp4-Cre Fto^flox/flox, fto-AKO) mice were fed with high-fat diet (60% fat in calories; Research Diets, D12492) for the desired periods of time, and food intake and body weight were measured every week after weaning (at 3 weeks of age).
Response Summary	Apoptosis regulator Bcl-2 (BCL2) acted as the target of METTL3, thereby regulating the proliferation and apoptosis of breast cancer.

Dentofacial anomalies [ICD-11: DA0E]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[10]
Responsed Disease	Temporomandibular joint disorders [ICD-11: DA0E.8]
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
	Autophagy			hsa04140
Cell Process	Cell proliferation and metastasis
	Cell apoptosis
In-vitro Model	ATDC-5	Mouse teratocarcinoma	Mus musculus	CVCL_3894
In-vivo Model	For MIA + SAH control, S-adenosylhomocysteine (SAH), Mettl3 inhibitor (10 mg/kg) (MCE, NJ, USA) was injected intraperitoneally before MIA injection and maintained twice a week until mice were sacrificed.
Response Summary	Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) induced temporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by TNF-alpha stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Apoptosis regulator Bcl-2 (BCL2) signal axis which provides promising therapeutic strategy for temporomandibular joint osteoarthritis.

Aspartate--tRNA ligase, cytoplasmic (DARS)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Liver	Mus musculus
Treatment: Mettl3 knockout liver Control: Wild type liver cells		GSE198513
Regulation		logFC: -5.90E-01 p-value: 7.45E-13
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.22E+00	GSE60213

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[13]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Pathway Response	Autophagy			hsa04140
Cell Process	Cell autophagy
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	End1/E6E7	Normal	Homo sapiens	CVCL_3684
	DoTc2 4510	Cervical carcinoma	Homo sapiens	CVCL_1181
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
Response Summary	DARS-AS1 was validated to facilitate DARS translation via recruiting METTL3 and METTL14, which bound with DARS mRNA Aspartate--tRNA ligase, cytoplasmic (DARS) mRNA 5' untranslated region (5'UTR) and promoting its translation. The present study demonstrated that the 'HIF1-Alpha/DARS-AS1/DARS/ATG5/ATG3' pathway regulated the hypoxia-induced cytoprotective autophagy of cervical cancer(CC) and is a promising target of therapeutic strategies for patients afflicted with CC.

ATP-binding cassette sub-family C member 9 (ABCC9)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	ARPE-19 cell line	Homo sapiens
Treatment: shMETTL3 ARPE-19 cells Control: shControl ARPE-19 cells		GSE202017
Regulation		logFC: -1.97E+00 p-value: 5.10E-08
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 6.69E+00	GSE60213

Nasopharyngeal carcinoma [ICD-11: 2B6B]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[14]
Responsed Disease	Nasopharyngeal carcinoma [ICD-11: 2B6B]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	ABC transporters			hsa02010
	Wnt signaling pathway			hsa04310
	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Ubiquitination degradation
In-vitro Model	CNE-1	Normal	Homo sapiens	CVCL_6888
	CNE-2	Nasopharyngeal carcinoma	Homo sapiens	CVCL_6889
In-vivo Model	A total of 2 × 10⁶ cells was mixed with 0.2 ml PBS (pH 7.4) and 30% (v/v) Matrigel matrix (BD Biosciences).
Response Summary	TRIM11 regulates nasopharyngeal carcinoma drug resistance by positively modulating the Daple/beta-catenin/ATP-binding cassette sub-family C member 9 (ABCC9) signaling pathway. TRIM11 enhanced the multidrug resistance in NPC by inhibiting apoptosis in vitro and promoting cisplatin (DDP) resistance in vivo. METTL3-mediated m6A modification caused the upregulation of TRIM11 via IGF2BP2 in NPC drug-resistant cells.

ATP-binding cassette sub-family D member 1 (ABCD1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shMETTL3 MOLM13 cells Control: MOLM13 cells		GSE98623
Regulation		logFC: -9.42E-01 p-value: 1.69E-05
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 8.82E+00	GSE60213

Renal cell carcinoma [ICD-11: 2C90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[15]
Responsed Disease	Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulation	Up regulation
Pathway Response	ABC transporters			hsa02010
Cell Process	Cell migration and spheroid formation
In-vitro Model	786-O	Renal cell carcinoma	Homo sapiens	CVCL_1051
In-vitro Model	A-498	Renal cell carcinoma	Homo sapiens	CVCL_1056
In-vivo Model	A498 cells (1 × 10⁶ cells) were resuspended in 100 uL of PBS and subcutaneously injected into the axillary fossa of nude mice (BALB/c-nude, 4 weeks old).
Response Summary	knockdown of METTL3 in clear cell renal cell carcinoma cell line impaired both cell migration capacity and tumor spheroid formation in soft fibrin gel, a mechanical method for selecting stem-cell-like tumorigenic cells. METTL3 knockdown cells and functional studies confirmed that translation of ATP-binding cassette sub-family D member 1 (ABCD1).

ATPase family AAA domain-containing protein 2 (ATAD2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	DKO-1 cell line	Homo sapiens
Treatment: METTL3 knockdown DKO-1 cell Control: DKO-1 cell		GSE182382
Regulation		logFC: 6.62E-01 p-value: 6.71E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.75E+00	GSE60213

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[16]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Up regulation
Cell Process	Cell proliferation and invasion
Cell Process	Cell apoptosis
In-vitro Model	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
Response Summary	METTL3 functions as an oncogene in the growth and invasion of osteosarcoma by regulating ATPase family AAA domain-containing protein 2 (ATAD2), suggesting a potential therapeutic target for osteosarcoma treatment.

Autophagy protein 5 (ATG5)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	CT26 cell line	Mus musculus
Treatment: METTL3 knockout CT26 cells Control: CT26 cells		GSE142589
Regulation		logFC: -9.09E-01 p-value: 4.91E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 8.30E+00	GSE60213

Enterovirus [ICD-11: 1A2Y]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[7]
Responsed Disease	Enterovirus [ICD-11: 1A2Y]
Target Regulation	Up regulation
Pathway Response	Autophagy	hsa04140
Cell Process	Cell proliferation and metastasis
	Cell apoptosis
	Cell autophagy
In-vitro Model	Schwann cells (A type of glial cell that surrounds neurons)
Response Summary	Knocking down METTL3 prevented Enterovirus 71-induced cell death and suppressed Enterovirus 71-induced expression of Bax while rescuing Bcl-2 expression after Enterovirus 71 infection. Knocking down METTL3 inhibited Enterovirus 71-induced expression of Autophagy protein 5 (ATG5), Atg7 and LC3 II. Knocking down METTL3 inhibited Enterovirus 71-induced apoptosis and autophagy.

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[17]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib	Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, Autophagy protein 5 (ATG5), ATG12, and ATG16L1.

Lung cancer [ICD-11: 2C25]

In total 3 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Chloroquine		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as Autophagy protein 5 (ATG5), ATG7, LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Gefitinib		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as Autophagy protein 5 (ATG5), ATG7, LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Experiment 3 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Beta-Elemen		Phase 3	Drug Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as Autophagy protein 5 (ATG5), ATG7, LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.

Testicular cancer [ICD-11: 2C80]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[19]
Responsed Disease	Testicular cancer [ICD-11: 2C80]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular Processes
	Cellular Transport
	Cellular catabolism
	Cell autophagy
In-vitro Model	Tcam-2/DDP (Cisplatin-resistant TCam-2 cell line)
	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012
Response Summary	m6A methyltransferase METTL3 regulates autophagy and sensitivity to cisplatin by targeting Autophagy protein 5 (ATG5) in seminoma. The use of autophagy inhibitors 3-MA could reverse the protective effect of METTL3 on TCam-2 cells.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[19]
Responsed Disease	Testicular cancer [ICD-11: 2C80]
Responsed Drug	3-Methyladenine		Investigative	Drug Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular Processes
	Cellular Transport
	Cellular catabolism
	Cell autophagy
In-vitro Model	Tcam-2/DDP (Cisplatin-resistant TCam-2 cell line)
	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012
Response Summary	m6A methyltransferase METTL3 regulates autophagy and sensitivity to cisplatin by targeting Autophagy protein 5 (ATG5) in seminoma. The use of autophagy inhibitors 3-MA could reverse the protective effect of METTL3 on TCam-2 cells.

Autophagy-related protein 16-1 (ATG16L1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	CT26 cell line	Mus musculus
Treatment: METTL3 knockout CT26 cells Control: CT26 cells		GSE142589
Regulation		logFC: -8.44E-01 p-value: 3.07E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.03E+00	GSE60213

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[17]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib	Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, ATG7, ATG12, and Autophagy-related protein 16-1 (ATG16L1).

Basic leucine zipper transcriptional factor ATF-like 2 (BATF2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	ARPE-19 cell line	Homo sapiens
Treatment: shMETTL3 ARPE-19 cells Control: shControl ARPE-19 cells		GSE202017
Regulation		logFC: -2.08E+00 p-value: 6.32E-06
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.91E+00	GSE60213

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[20]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation
Pathway Response	p53 signaling pathway			hsa04115
In-vitro Model	SNU-216	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_3946
In-vitro Model	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
In-vivo Model	A total of 5 × 10⁶ stably transfected HGC-27 cells were subcutaneously injected into the right axillary fossa of nude mice. Tumor volume was measured every 3 days and calculated with the following formula: V = (L × W2)/2 cm² (V, tumor volume; L, length; W, width). The mice were sacrificed at 3-4 weeks after injection, and the tumors were weighed. For the lung metastasis model, 5 × 10⁶ stably transfected HGC-27 cells were injected into the tail veins of nude mice. Forty-five days later, the mice were sacrificed, and the lungs were dissected to examine the histopathological metastatic loci. The peritoneal dissemination ability of GC cells was evaluated via intraperitoneal injection. A total of 5 × 10⁶ stably transfected HGC-27 cells in 500 uL of PBS were injected into the peritoneal cavity of BALB/c nude mice. Mice were carefully monitored until they were killed at 4 weeks, at which point peritoneal metastases were examined and recorded.
Response Summary	N6-methyladenosine (m6A) modification of Basic leucine zipper transcriptional factor ATF-like 2 (BATF2) mRNA by METTL3 repressed its expression in gastric cancer.

Beta-catenin-interacting protein 1 (CTNNBIP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -1.02E+00 p-value: 3.20E-17
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.17E+00	GSE60213

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[21]
Responsed Disease	Glioma [ICD-11: 2A00.0]
Target Regulation	Up regulation
In-vitro Model	T98G	Glioblastoma	Homo sapiens	CVCL_0556
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	LN-18	Glioblastoma	Homo sapiens	CVCL_0392
	HEB (human normal glial cell line HEB were obtained from Tongpai (Shanghai) biotechnology co., LTD (Shanghai, China))
	A-172	Glioblastoma	Homo sapiens	CVCL_0131
Response Summary	METTL3-mediated m6A modification upregulated circDLC1 expression, and circDLC1 promoted Beta-catenin-interacting protein 1 (CTNNBIP1) transcription by sponging miR-671-5p, thus repressing the malignant proliferation of glioma.

Broad substrate specificity ATP-binding cassette transporter ABCG2 (BCRP/ABCG2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -9.03E-01 p-value: 2.29E-02
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 4.88E+00	GSE60213

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[22]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulation	Up regulation
Cell Process	Cell growth and death
	Cell apoptosis
In-vitro Model	ADR-resistant MCF-7 (MCF-7/ADR) cells (Human breast cancer doxorubicin-resistant cell line)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
In-vivo Model	Cell suspensions (2 × 10⁶ cells/mL) made with MCF-7/ADR cells stably expressing METTL3 and/or miR-221-3p inhibitor were subcutaneously implanted into each mouse. One week later, xenografted mice were injected with 0.1 mL ADR (25 mg/kg, intraperitoneal injection) twice a week.
Response Summary	METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating pri-microRNA-221-3p maturation in a m6A-dependent manner. METTL3 knockdown was shown to reduce the expression of miR-221-3p by reducing pri-miR-221-3p m6A mRNA methylation, reducing the expression of MDR1 and Broad substrate specificity ATP-binding cassette transporter ABCG2 (BCRP/ABCG2), and inducing apoptosis. Identified the METTL3/miR-221-3p/HIPK2/Che-1 axis as a novel signaling event that will be responsible for resistance of BC cells to ADR.

Cadherin-1 (CDH1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -7.84E-01 p-value: 1.59E-117
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 4.00E+00	GSE60213

Idiopathic interstitial pneumonitis [ICD-11: CB03]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[23]
Responsed Disease	Pulmonary Fibrosis [ICD-11: CB03.4]
Pathway Response	Adherens junction	hsa04520
Cell Process	Epithelial-mesenchymal transition
Response Summary	PM2.5 exposure increased the levels of METTL3-mediated m6A modification of Cadherin-1 (CDH1) mRNA. PM2.5 exposure triggered EMT progression to promote the pulmonary fibrosis via miR-494-3p/YTHDF2 recognized and METTL3 mediated m6A modification.

Cadherin-2 (CDH2/N-cadherin)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 8.67E-01 p-value: 3.90E-33
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 4.52E+00	GSE60213

Nasopharyngeal carcinoma [ICD-11: 2B6B]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[24]
Responsed Disease	Nasopharyngeal carcinoma [ICD-11: 2B6B]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	Neural progenitor cells (NPCs) (The progenitor cells of the CNS)
	NP69 (A human immortalized nasopharyngeal epithelial)
	HNE-2	Nasopharyngeal carcinoma	Homo sapiens	CVCL_FA07
	HNE-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_0308
	CNE-2	Nasopharyngeal carcinoma	Homo sapiens	CVCL_6889
	CNE-1	Normal	Homo sapiens	CVCL_6888
In-vivo Model	1 × 10⁵ HNE2 cells (with or without METTL3 knockdown) were labeled with luciferase gene and injected into the tail vein of the nude mice.
Response Summary	METTL3 activated the luciferase activity of TOPflash (a reporter for beta-catenin/TCF signaling), and downregulation of METTL3 inhibited the expression of beta-catenin/TCF target genes vimentin and Cadherin-2 (CDH2/N-cadherin), which are two regulators of epithelial-mesenchymal transition. METTL3 silencing decreased the m6A methylation and total mRNA levels of Tankyrase, a negative regulator of axin. METTL3 is a therapeutic target for NPC.

Melanoma [ICD-11: 2C30]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[1]
Responsed Disease	Melanoma [ICD-11: 2C30]
Target Regulation	Up regulation
Cell Process	Cell invasion/migration
In-vitro Model	451Lu	Cutaneous melanoma	Homo sapiens	CVCL_6357
	A-375	Amelanotic melanoma	Homo sapiens	CVCL_0132
	A375-MA2	Amelanotic melanoma	Homo sapiens	CVCL_X495
	MeWo	Cutaneous melanoma	Homo sapiens	CVCL_0445
	SK-MEL-2	Melanoma	Homo sapiens	CVCL_0069
	WM164	Cutaneous melanoma	Homo sapiens	CVCL_7928
	WM3211	Acral lentiginous melanoma	Homo sapiens	CVCL_6797
	WM3918	Melanoma	Homo sapiens	CVCL_C279
	WM793	Melanoma	Homo sapiens	CVCL_8787
Response Summary	METTL3 is upregulated in human melanoma and plays a role in invasion/migration through MMP2. METTL3 overexpression promotes accumulation of MMP2 and Cadherin-2 (CDH2/N-cadherin) in melanoma cells.

Catenin beta-1 (CTNNB1/Beta-catenin)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Embryonic stem cells	Mus musculus
Treatment: METTL3 knockout mESCs Control: Wild type mESCs		GSE156481
Regulation		logFC: -8.46E-01 p-value: 2.97E-40
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.37E+00	GSE60213

Nasopharyngeal carcinoma [ICD-11: 2B6B]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[24]
Responsed Disease	Nasopharyngeal carcinoma [ICD-11: 2B6B]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	Neural progenitor cells (NPCs) (The progenitor cells of the CNS)
	NP69 (A human immortalized nasopharyngeal epithelial)
	HNE-2	Nasopharyngeal carcinoma	Homo sapiens	CVCL_FA07
	HNE-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_0308
	CNE-2	Nasopharyngeal carcinoma	Homo sapiens	CVCL_6889
	CNE-1	Normal	Homo sapiens	CVCL_6888
In-vivo Model	1 × 10⁵ HNE2 cells (with or without METTL3 knockdown) were labeled with luciferase gene and injected into the tail vein of the nude mice.
Response Summary	METTL3 activated the luciferase activity of TOPflash (a reporter for beta-catenin/TCF signaling), and downregulation of METTL3 inhibited the expression of Catenin beta-1 (CTNNB1/Beta-catenin)/TCF target genes vimentin and N-cadherin, which are two regulators of epithelial-mesenchymal transition. METTL3 silencing decreased the m6A methylation and total mRNA levels of Tankyrase, a negative regulator of axin. METTL3 is a therapeutic target for NPC.

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[25]
Responsed Disease	Hepatoblastoma [ICD-11: 2C12.01]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	RNA stability
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	QSG-7701	Endocervical adenocarcinoma	Homo sapiens	CVCL_6944
In-vivo Model	5 × 10⁶ cells were subcutaneously injected into the left or right flank of each mouse.
Response Summary	METTL3 is significantly up-regulated in Hepatoblastoma(HB) and promotes HB development.m6A mRNA methylation contributes significantly to regulate the Wnt/beta-catenin pathway. Reduced m6A methylation can lead to a decrease in expression and stability of the Catenin beta-1 (CTNNB1/Beta-catenin).

Spina bifida [ICD-11: LA02]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[26]
Responsed Disease	Neural tube defect [ICD-11: LA02.Z]
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Cell apoptosis
In-vitro Model	HT22	Normal	Mus musculus	CVCL_0321
In-vivo Model	The mice were maintained on a 12-h light/dark cycle (lights on from 8:00 a.m. to 8:00 p.m.). On day 7.5 of pregnancy (E7.5), ethionine (Sigma-Aldrich, USA) was intraperitoneally injected only once at a dose of 500 mg/kg to establish the NTDs embryo model. And SAM (MedChemExpress, USA) was intraperitoneally injected only once at a dose of 30 mg/kg. The same dose was intraperitoneally injected to the pregnant mice for control group.
Response Summary	SAM not only played a compensatory role, but also led to m6A modification changes in neural tube development and regulation. Ethionine affected m6A modification by reducing SAM metabolism. METTL3 is enriched in HT-22 cells, and METTL3 knockdown reduces cell proliferation and increases apoptosis through suppressing Wnt/Catenin beta-1 (CTNNB1/Beta-catenin) signaling pathway. Overexpression of ALKBH5 can only inhibit cell proliferation, but cannot promote cell apoptosis.

Cellular tumor antigen p53 (TP53/p53)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HeLa cell line	Homo sapiens
Treatment: METTL3 knockdown HeLa cells Control: HeLa cells		GSE70061
Regulation		logFC: 1.12E+00 p-value: 1.48E-02
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.05E+00	GSE60213

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[27]
Responsed Disease	Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Responsed Drug	Arsenite		Phase 2	Drug Info
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
In-vitro Model	HaCaT	Normal	Homo sapiens	CVCL_0038
Response Summary	METTL3 significantly decreased m6A level, restoring Cellular tumor antigen p53 (TP53/p53) activation and inhibiting cellular transformation phenotypes in the arsenite-transformed cells. m6A downregulated the expression of the positive p53 regulator, PRDM2, through the YTHDF2-promoted decay of PRDM2 mRNAs. m6A upregulated the expression of the negative p53 regulator, YY1 and MDM2 through YTHDF1-stimulated translation of YY1 and MDM2 mRNA. This study further sheds light on the mechanisms of arsenic carcinogenesis via RNA epigenetics.

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[28]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Down regulation
Pathway Response	p53 signaling pathway			hsa04115
	Cell cycle			hsa04110
	Apoptosis			hsa04210
Cell Process	Cell apoptosis
Cell Process	Cells in G3/M phase decreased
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	MOLT-4	Adult T acute lymphoblastic leukemia	Homo sapiens	CVCL_0013
	Kasumi-1	Myeloid leukemia with maturation	Homo sapiens	CVCL_0589
	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	HL-60	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	HEL	Erythroleukemia	Homo sapiens	CVCL_0001
	CCRF-CEM C7	T acute lymphoblastic leukemia	Homo sapiens	CVCL_6825
	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	METTL3 and METTL14 play an oncogenic role in acute myeloid leukemia(AML) by targeting mdm2/Cellular tumor antigen p53 (TP53/p53) signal pathway. The knockdown of METTL3 and METTL14 in K562 cell line leads to several changes in the expression of p53 signal pathway, including the upregulation of p53, cyclin dependent kinase inhibitor 1A (CDKN1A/p21), and downregulation of mdm2.

Colon cancer [ICD-11: 2B90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[29]
Responsed Disease	Colon cancer [ICD-11: 2B90]
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
Cell Process	Protein signaling
In-vitro Model	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In-vitro Model	WiDr	Colon adenocarcinoma	Homo sapiens	CVCL_2760
Response Summary	The produced p53 R273H mutant protein resulted in acquired multidrug resistance in colon cancer cells. Either silencing METTL3 expression by using small interfering RNA (siRNA) or inhibiting RNA methylation with neplanocin A suppressed m6A formation in Cellular tumor antigen p53 (TP53/p53) pre-mRNA, and substantially increased the level of phosphorylated p53 protein (Ser15) and its function in cells heterozygously carrying the R273H mutation, thereby re-sensitizing these cells to anticancer drugs.

Liver cancer [ICD-11: 2C12]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[30]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Apatinib		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	QGY-7701	Human papillomavirus-related endocervical adenocarcinoma	Homo sapiens	CVCL_6859
	HHL-5	Normal	Homo sapiens	CVCL_S956
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Nude mice (4-6 week-old) were administered sterile water and feed in a specific pathogen-free barrier. Using a 1-mL syringe, 1 × 10⁷ HEPG2 cells were subcutaneously inoculated into the right axilla of nude mice to build the HCC xenograft model. When the tumor volume reached 50 mm3, the nude mice were randomly divided into 1 control (n = 4) and 3 treatment groups (n = 4 each). RG7112, apatinib, and RG7112 + apatinib were administered to the treatment groups and an equal volume of dimethyl sulfoxide to the control group by daily gavage for 14 d. The tumor length (L) and width (W) were measured on alternate days using vernier calipers. The following formula was used to calculate the tumor volume: volume (mm3) = 0.5 × L × W × W. At the end of the experiment, the nude mice were killed by CO2 overdose anesthesia. The tumors were dissected and weighed using a precision balance, and the tumor tissue was stored in liquid nitrogen for further analysis.
Response Summary	Cellular tumor antigen p53 (TP53/p53) n6-methyladenosine (m6A) played a decisive role in regulating Hepatocellular carcinoma(HCC) sensitivity to chemotherapy via the p53 activator RG7112 and the vascular endothelial growth factor receptor inhibitor apatinib. p53 mRNA m6A modification blockage induced by S-adenosyl homocysteine or siRNA-mediated METTL3 inhibition enhanced HCC sensitivity to chemotherapy.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[30]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	RG7112		Phase 1	Drug Info
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	QGY-7701	Human papillomavirus-related endocervical adenocarcinoma	Homo sapiens	CVCL_6859
	HHL-5	Normal	Homo sapiens	CVCL_S956
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Nude mice (4-6 week-old) were administered sterile water and feed in a specific pathogen-free barrier. Using a 1-mL syringe, 1 × 10⁷ HEPG2 cells were subcutaneously inoculated into the right axilla of nude mice to build the HCC xenograft model. When the tumor volume reached 50 mm3, the nude mice were randomly divided into 1 control (n = 4) and 3 treatment groups (n = 4 each). RG7112, apatinib, and RG7112 + apatinib were administered to the treatment groups and an equal volume of dimethyl sulfoxide to the control group by daily gavage for 14 d. The tumor length (L) and width (W) were measured on alternate days using vernier calipers. The following formula was used to calculate the tumor volume: volume (mm3) = 0.5 × L × W × W. At the end of the experiment, the nude mice were killed by CO2 overdose anesthesia. The tumors were dissected and weighed using a precision balance, and the tumor tissue was stored in liquid nitrogen for further analysis.
Response Summary	Cellular tumor antigen p53 (TP53/p53) n6-methyladenosine (m6A) played a decisive role in regulating Hepatocellular carcinoma(HCC) sensitivity to chemotherapy via the p53 activator RG7112 and the vascular endothelial growth factor receptor inhibitor apatinib. p53 mRNA m6A modification blockage induced by S-adenosyl homocysteine or siRNA-mediated METTL3 inhibition enhanced HCC sensitivity to chemotherapy.

Collagen alpha-1 (III) chain (COL3A1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: 2.13E+00 p-value: 6.01E-268
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 3.39E+00	GSE60213

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[31]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Down regulation
In-vitro Model	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
Response Summary	METTL3 could down-regulate the expression of Collagen alpha-1 (III) chain (COL3A1) by increasing its m6A methylation, ultimately inhibiting the metastasis of TNBC cells.

Collagenase 3 (MMP13)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	DKO-1 cell line	Homo sapiens
Treatment: METTL3 knockdown DKO-1 cell Control: DKO-1 cell		GSE182382
Regulation		logFC: 9.33E-01 p-value: 3.02E-02
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 4.73E+00	GSE60213

Osteoarthritis [ICD-11: FA05]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[32]
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulation	Up regulation
Cell Process	Inflammatory response and apoptosis
In-vitro Model	ATDC-5	Mouse teratocarcinoma	Mus musculus	CVCL_3894
In-vivo Model	The right knee joint of each OA mouse was injected with 1U of type VII collagenase over two consecutive days to obtain experimental OA joint, and the control mice received the equal volume of physiological saline.
Response Summary	METTL3 has a functional role in mediates osteoarthritis progression by regulating NF-Kappa-B signaling and ECM synthesis in chondrocytes that shed insight on developing preventive and curative strategies for OA by focusing on METTL3 and mRNA methylation. Silencing of METTL3 promotes degradation of extracellular matrix (ECM) by reducing the expression of Collagenase 3 (MMP13) and Coll X, elevating the expression of Aggrecan and Coll II.

CUB domain-containing protein 1 (CDCP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 6.56E-01 p-value: 5.99E-11
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.49E+00	GSE60213

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[34]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Up regulation
In-vitro Model	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	RWPE-1	Normal	Homo sapiens	CVCL_3791
	NSTC2 (Nickel-induced transformation of human cells)
	MC-SV-HUC T-2	Ureteral tumor cell	Homo sapiens	CVCL_6418
	16HBE14o-	Normal	Homo sapiens	CVCL_0112
In-vivo Model	To test for malignant transformation, 1×10⁷ cells were inoculated subcutaneously in the dorsal thoracic midline of ten NOD/SCID mice (Weitong Lihua Experimental Animal Technology Co. Ltd). Tumor formation and growth were assessed every 3 days.
Response Summary	m6A methyltransferase METTL3 and demethylases ALKBH5 mediate the m6A modification in 3'-UTR of CDCP1 mRNA. METTL3 and CUB domain-containing protein 1 (CDCP1) are upregulated in the bladder cancer patient samples and the expression of METTL3 and CDCP1 is correlated with the progression status of the bladder cancers.

Cyclin-dependent kinase inhibitor 1 (CDKN1A)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 7.88E-01 p-value: 3.07E-21
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 9.39E+00	GSE60213

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[28]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell apoptosis
Cell Process	Cells in G4/M phase decreased
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	MOLT-4	Adult T acute lymphoblastic leukemia	Homo sapiens	CVCL_0013
	Kasumi-1	Myeloid leukemia with maturation	Homo sapiens	CVCL_0589
	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	HL-60	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	HEL	Erythroleukemia	Homo sapiens	CVCL_0001
	CCRF-CEM C7	T acute lymphoblastic leukemia	Homo sapiens	CVCL_6825
	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	METTL3 and METTL14 play an oncogenic role in acute myeloid leukemia(AML) by targeting mdm2/p53 signal pathway. The knockdown of METTL3 and METTL14 in K562 cell line leads to several changes in the expression of p53 signal pathway, including the upregulation of p53, cyclin dependent kinase inhibitor 1A (CDKN1A/Cyclin-dependent kinase inhibitor 1 (CDKN1A)), and downregulation of mdm2.

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[36]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Down regulation
In-vitro Model	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	SUM1315MO2	Invasive breast carcinoma of no special type	Homo sapiens	CVCL_5589
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
	HBL-100	Normal	Homo sapiens	CVCL_4362
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
In-vivo Model	About 1 × 10⁷ stable METTL3 overexpression and negative control SUM-1315 cells were injected subcutaneously into the axilla of the female BALB/C nude mice (4-6 weeks old, 18-20 g, 10 mice/group). One week after injection, the two groups, METTL3 OE and NC, were then randomly allocated into the control group and experimental group (5 mice/group), which were treated with PBS or metformin (250 mg/kg/dose, respectively). PBS or metformin was administered every 2 days via intraperitoneal injection.
Response Summary	METTL3 is able to promote breast cancer cell proliferation by regulating the Cyclin-dependent kinase inhibitor 1 (CDKN1A) expression by an m6A-dependent manner. Metformin can take p21 as the main target to inhibit such effect.

Oral cavity/oesophagus/stomach in situ carcinoma [ICD-11: 2E60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[37]
Responsed Disease	Esophageal squamous cell carcinoma [ICD-11: 2B70.1]
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Arrest cell cycle at G2/M phase
In-vitro Model	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
In-vitro Model	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
In-vivo Model	Totally 5 × 10⁶ ESCC cells after treatment were administered to randomized animals by the subcutaneous route (right flank) in 200 uL DMEM. Tumor measurement was performed every other day. At study end (at least 3 weeks), the animals underwent euthanasia, and the tumors were extracted for histology.
Response Summary	METTL3 modulates the cell cycle of Esophageal squamous cell carcinoma(ESCC) cells through a Cyclin-dependent kinase inhibitor 1 (CDKN1A)-dependent pattern. METTL3-guided m6A modification contributes to the progression of ESCC via the p21-axis.

Cytochrome P450 1B1 (CYP1B1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: 1.33E+00 p-value: 1.93E-05
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.72E+00	GSE60213

Urinary/pelvic organs injury [ICD-11: NB92]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[38]
Responsed Disease	Injury of kidney [ICD-11: NB92.0]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	NRK-52E	Normal	Rattus norvegicus	CVCL_0468
In-vivo Model	Rats were anesthetized and incised through the midline of the abdomen, and the left renal vertebral arch and arteries were blocked for 45 min, thereby resulting in left kidney ischemia. At the same time, the right kidney was removed, further aggravating the degree of left kidney injury.
Response Summary	METTL3 contributes to renal ischemia-reperfusion injury by regulating Foxd1 methylation. When METTL3 was inhibited, m6A levels were accordingly decreased and cell apoptosis was suppressed in the H/R in vitro model. Based on MeRIP sequencing, transcription factor activating enhancer binding protein 2-alpha (tfap2a), Cytochrome P450 1B1 (CYP1B1), and forkhead box D1 (foxd1) were significantly differentially expressed, as was m6A, which is involved in the negative regulation of cell proliferation and kidney development.

Death-associated protein kinase 2 (DAPK2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -2.25E+00 p-value: 1.26E-07
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 6.83E+00	GSE60213

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[39]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Down regulation
In-vitro Model	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	The nude mice were maintained under pathogen-free conditions and kept under timed lighting conditions mandated by the committee with food and water provided ad libitum. For xenograft experiments, nude mice were injected subcutaneously with 5 × 10⁶ cells resuspended in 0.1 mL PBS. When a tumor was palpable, it was measured every 3 days.
Response Summary	Cigarette smoking induced aberrant N6-methyladenosine modification of Death-associated protein kinase 2 (DAPK2), which resulted in decreased DAPK2 mRNA stability and expression of its mRNA and protein. This modification was mediated by the m6A "writer" METTL3 and the m6A "reader" YTHDF2. BAY 11-7085, a NF-Kappa-B signaling selective inhibitor, was shown to efficiently suppressed downregulation of DAPK2-induced oncogenic phenotypes of NSCLC cells.

Developmentally-regulated GTP-binding protein 1 (DRG1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Pancreatic islets	Mus musculus
Treatment: Mettl3 knockout mice Control: Mettl3 flox/flox mice		GSE155612
Regulation		logFC: 6.62E-01 p-value: 3.32E-04
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.01E+01	GSE60213

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[40]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Up regulation
Cell Process	Cell cycle
Cell Process	Cell apoptosis
In-vitro Model	143B	Osteosarcoma	Homo sapiens	CVCL_2270
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
Response Summary	ELAVL1 knockdown impaired the stability of DRG1 mRNA, thereby reducing both the mRNA and protein levels of Developmentally-regulated GTP-binding protein 1 (DRG1). In all, DRG1 exerted tumorigenic effects in osteosarcoma, and the up-regulation of DRG1 in OS was induced by METTL3 and ELAVL1 in an m6A-dependent manner.

DNA polymerase kappa (Pol Kappa/POLK)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 8.09E-01 p-value: 1.19E-26
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.90E+00	GSE60213

Exposure to radiation [ICD-11: PH73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[41]
Responsed Disease	Exposure to radiation [ICD-11: PH73]
Target Regulation	Up regulation
Cell Process	DNA repair
Cell Process	Nucleotide excision repair (hsa03420)
In-vitro Model	A-375	Amelanotic melanoma	Homo sapiens	CVCL_0132
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	MEF (Mouse embryonic fibroblasts)
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
Response Summary	Methylation at the 6 position of adenosine (m6A) in RNA is rapidly (within 2 min) and transiently induced at DNA damage sites in response to ultraviolet irradiation. This modification occurs on numerous poly(A)+ transcripts and is regulated by the methyltransferase METTL3 and the demethylase FTO. DNA DNA polymerase kappa (Pol Kappa/POLK), which has been implicated in both nucleotide excision repair and trans-lesion synthesis, required the catalytic activity of METTL3 for immediate localization to ultraviolet-induced DNA damage sites.

DNA replication licensing factor MCM6 (MCM6)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Liver	Mus musculus
Treatment: Mettl3-deficient liver Control: Wild type liver cells		GSE197800
Regulation		logFC: 2.47E+00 p-value: 3.65E-08
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.92E+00	GSE60213

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[42]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	GES-1	Normal	Homo sapiens	CVCL_EQ22
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
	MKN74	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_2791
	pGCC (Primary GC cells)
	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
In-vivo Model	A total of 2 × 10⁶ GC cells were injected into the flank of nude mice in a 1:1 suspension of BD Matrigel (BD Biosciences) in phosphate-buffered saline (PBS) solution.
Response Summary	In gastric cancer, several component molecules (e.g., MCM5, DNA replication licensing factor MCM6 (MCM6), etc.) of MYC target genes were mediated by METTL3 via altered m6A modification.

E3 ubiquitin-protein ligase TRIM7 (TRIM7)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	ARPE-19 cell line	Homo sapiens
Treatment: shMETTL3 ARPE-19 cells Control: shControl ARPE-19 cells		GSE202017
Regulation		logFC: -1.54E+00 p-value: 1.28E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 7.18E+00	GSE60213

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[43]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Down regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Proteasome pathway degradation
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
In-vivo Model	MG63 cells transduced with lentivirus expressing shTRIM7 or shNC, and SAOS2 cells transduced with lentivirus expressing TRIM7, BRMS1, TRIM7 plus BRMS1 or control vector, were injected via the tail vein into the nude mice (1 × 10⁶ cells/mouse) (n = 11 per group).
Response Summary	E3 ubiquitin-protein ligase TRIM7 (TRIM7) mRNA stability was regulated by the METTL3/14-YTHDF2-mRNA in a decay-dependent manner. TRIM7 plays a key role in regulating metastasis and chemoresistance in osteosarcoma through ubiquitination of BRMS1.

eIF4E-binding protein 1 (4EBP1/EIF4EBP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shMETTL3 MOLM13 cells Control: MOLM13 cells		GSE98623
Regulation		logFC: 8.71E-01 p-value: 3.32E-08
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 9.71E+00	GSE60213

Retina cancer [ICD-11: 2D02]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[44]
Responsed Disease	Retinoblastoma [ICD-11: 2D02.2]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
	mTOR signaling pathway			hsa04150
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	WERI-Rb-1	Retinoblastoma	Homo sapiens	CVCL_1792
	Y-79	Retinoblastoma	Homo sapiens	CVCL_1893
In-vivo Model	To establish a subcutaneous tumour model in nude mice, 2 × 10⁷ Y79 cells (METTL3 knockdown group: shNC, shRNA1 and shRNA2; METTL3 up-regulated group: NC and METLL3) were resuspended in 1 mL of pre-cooled PBS, and 200 uL of the cell suspension was injected subcutaneously into the left side of the armpit to investigate tumour growth (4 × 10⁶ per mouse).
Response Summary	METTL3 promotes the progression of retinoblastoma through PI3K/AKT/mTOR pathways in vitro and in vivo. METTL3 has an impact on the PI3K-AKT-mTOR-P70S6K/eIF4E-binding protein 1 (4EBP1/EIF4EBP1) pathway. The cell proliferation results show that the stimulatory function of METTL3 is lost after rapamycin treatment.

Endoplasmic reticulum chaperone BiP (Grp78)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	ARPE-19 cell line	Homo sapiens
Treatment: shMETTL3 ARPE-19 cells Control: shControl ARPE-19 cells		GSE202017
Regulation		logFC: -9.73E-01 p-value: 3.50E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.24E+00	GSE60213

Diseases of the musculoskeletal system [ICD-11: FC0Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[45]
Responsed Disease	Diseases of the musculoskeletal system [ICD-11: FC0Z]
Target Regulation	Down regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	RNA stability
In-vitro Model	MC3T3-E1	Normal	Mus musculus	CVCL_0409
Response Summary	METTL3 knockdown enhanced Endoplasmic reticulum chaperone BiP (Grp78) expression through YTHDF2-mediated RNA degradation, which elicited ER stress, thereby promoting osteoblast apoptosis and inhibiting cell proliferation and differentiation under LPS-induced inflammatory condition.

Ephrin type-A receptor 2 (EphA2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: 6.09E-01 p-value: 1.09E-18
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.66E+00	GSE60213

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[46]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	NCM460	Normal	Homo sapiens	CVCL_0460
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
In-vivo Model	A total of 8 × 10⁶ wild-type (WT) or METTL3-knockdown cells were injected into the dorsal flanks of 6-week-old nude mice. Seven mice were randomly selected to calculate the volume according to the following formula: V = (width2 × length)/2. Mice were euthanized three weeks after injection and tumors removed, weighed, fixed, and embedded for immunohistochemical analysis.
Response Summary	Ephrin type-A receptor 2 (EphA2) and VEGFA targeted by METTL3 via different IGF2BP-dependent mechanisms were found to promote vasculogenic mimicry (VM) formation via PI3K/AKT/mTOR and ERK1/2 signaling in CRC.

Far upstream element-binding protein 1 (FUBP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	DKO-1 cell line	Homo sapiens
Treatment: METTL3 knockdown DKO-1 cell Control: DKO-1 cell		GSE182382
Regulation		logFC: 6.14E-01 p-value: 4.72E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.31E+00	GSE60213

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[47]
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulation	Up regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0608
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HOP-62	Lung adenocarcinoma	Homo sapiens	CVCL_1285
In-vivo Model	For the in vivo tumorigenicity assay, female BALB/c nude mice (ages 4-5 weeks) were randomly divided into two groups (n = 6/group). Calu1 cells (4 × 10⁶) that had been stably transfected with sh-LCAT3 or scramble were implanted subcutaneously into the nude mice. Tumor growth was measured after one week, and tumor volumes were calculated with the following formula: Volume (cm³) = (length × width²)/2. After four weeks, the mice were euthanized, and the tumors were collected and weighed. For the in vivo tumor invasion assay, 1.2 × 10⁶ scramble or shLCAT3 cells were injected intravenously into the tail vein of nude mice (n = 6/group). 1.5 mg luciferin (Gold Biotech, St Louis, MO, USA) was administered once a week for 4 weeks, to monitor metastases using an IVIS@ Lumina II system (Caliper Life Sciences, Hopkinton, MA, USA).
Response Summary	LCAT3 upregulation is attributable to N6-methyladenosine (m6A) modification mediated by methyltransferase like 3 (METTL3), leading to LCAT3 stabilization. LCAT3 as a novel oncogenic lncRNA in the lung, and validated the LCAT3-Far upstream element-binding protein 1 (FUBP1)-MYC axis as a potential therapeutic target for lung adenocarcinomas.

Fatty acid synthase (FASN)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LNCaP cell line	Homo sapiens
Treatment: shMETTL3 LNCaP cells Control: shControl LNCaP cells		GSE147884
Regulation		logFC: -6.03E-01 p-value: 2.01E-249
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.26E+00	GSE60213

Type 2 diabetes mellitus [ICD-11: 5A11]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[48]
Responsed Disease	Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulation	Up regulation
Pathway Response	Insulin resistance			hsa04931
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3^fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3^fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3^fl/fl) were used for experiments.
Response Summary	Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (FASN), subsequently inhibited fatty acid metabolism. The expression of Acc1, Acly, Dgat2, Ehhadh, Fasn, Foxo, Pgc1a and Sirt1, which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.

Forkhead box protein D1 (FOXD1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 8.07E-01 p-value: 2.88E-13
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 6.40E+00	GSE60213

Urinary/pelvic organs injury [ICD-11: NB92]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[38]
Responsed Disease	Injury of kidney [ICD-11: NB92.0]
Target Regulation	Down regulation
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	NRK-52E	Normal	Rattus norvegicus	CVCL_0468
In-vivo Model	Rats were anesthetized and incised through the midline of the abdomen, and the left renal vertebral arch and arteries were blocked for 45 min, thereby resulting in left kidney ischemia. At the same time, the right kidney was removed, further aggravating the degree of left kidney injury.
Response Summary	METTL3 contributes to renal ischemia-reperfusion injury by regulating Forkhead box protein D1 (FOXD1) methylation. When METTL3 was inhibited, m6A levels were accordingly decreased and cell apoptosis was suppressed in the H/R in vitro model. Based on MeRIP sequencing, transcription factor activating enhancer binding protein 2-alpha (tfap2a), cytochrome P-450 1B1 (cyp1b1), and forkhead box D1 (foxd1) were significantly differentially expressed, as was m6A, which is involved in the negative regulation of cell proliferation and kidney development.

G1/S-specific cyclin-E1 (CCNE1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -1.64E+00 p-value: 3.22E-09
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 6.94E+00	GSE60213

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[49]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell proliferation
	Arrest cell cycle at G1 phase
In-vitro Model	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
In-vivo Model	LoVo cells (5 × 10⁶ cells/ 200 uL PBS) stably transfected with METTL3 knockdown lentiviral vector or control vector were respectively injected subcutaneously into the left flank of each mouse.
Response Summary	METTL3 promotes colorectal cancer proliferation by stabilizing G1/S-specific cyclin-E1 (CCNE1) mRNA in an m6A-dependent manner, representing a promising therapeutic strategy for the treatment of CRC.

H/ACA ribonucleoprotein complex subunit DKC1 (DKC1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Pancreatic islets	Mus musculus
Treatment: Mettl3 knockout mice Control: Mettl3 flox/flox mice		GSE155612
Regulation		logFC: 6.68E-01 p-value: 1.04E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.61E+00	GSE60213

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[50]
Responsed Disease	Liver cancer [ICD-11: 2C12]
Target Regulation	Down regulation
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
In-vivo Model	Athymic BALB/c mice were injected with LCSC cells at the armpit area subcutaneously. The mice were then sacrificed and the tumors recovered.
Response Summary	CircMEG3 inhibits the expression of m6A methyltransferase METTL3 dependent on HULC. Moreover, CircMEG3 inhibits the expression of H/ACA ribonucleoprotein complex subunit DKC1 (DKC1), a component of telomere synthetase H/ACA ribonucleoprotein (RNP; catalyst RNA pseudouracil modification) through METTL3 dependent on HULC. These observations provide important basic information for finding effective liver cancer therapeutic targets.

Heat shock protein HSP 90-alpha (HSP90/HSP90AA1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HUVEC cell line	Homo sapiens
Treatment: shMETTL3 HUVEC cells Control: shScramble HUVEC cells		GSE157544
Regulation		logFC: 6.51E-01 p-value: 1.12E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.19E+00	GSE60213

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[51]
Responsed Disease	Glioma [ICD-11: 2A00.0]
Target Regulation	Down regulation
Cell Process	Cell migration and proliferation
In-vitro Model	U251 (Fibroblasts or fibroblast like cells)
Response Summary	m6A regulated cell proliferation by influencing apoptosis of U251 cells through regulating Heat shock protein HSP 90-alpha (HSP90/HSP90AA1) expression. m6A level was decreased in glioma tissue, which was caused by decreased METTL3 and increased FTO levels.

Hepatocyte nuclear factor 1-alpha (HNF1A/TCF1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -1.64E+00 p-value: 4.47E-50
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 6.55E+00	GSE60213

Thyroid Cancer [ICD-11: 2D10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[52]
Responsed Disease	Thyroid Cancer [ICD-11: 2D10]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Cell migratory
In-vitro Model	B-CPAP	Thyroid gland carcinoma	Homo sapiens	CVCL_0153
	Nthy-ori 3-1	Normal	Homo sapiens	CVCL_2659
	TPC-1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
Response Summary	Silence of METTL3 inhibited migratory ability and Wnt activity in TPC-1 cells. METTL3 positively regulated the enrichment abundance of Hepatocyte nuclear factor 1-alpha (HNF1A/TCF1) in anti-IGF2BP2. TCF1 was responsible for METTL3-regulated thyroid carcinoma progression via the m6A methylation.

Hepatoma-derived growth factor (HDGF)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -6.20E-01 p-value: 6.85E-14
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.03E+00	GSE60213

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[53]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Pathway Response	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glycolysis
In-vitro Model	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
	NCI-N87	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_1603
	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
In-vivo Model	Mice 8 weeks after splenic portal vein injection of BGC823 cells with METTL3 overexpression or vector-transfected cells.
Response Summary	Elevated METTL3 expression promotes tumour angiogenesis and glycolysis in Gastric cancer. P300-mediated H3K27 acetylation activation in the promoter of METTL3 induced METTL3 transcription, which stimulated m6A modification of Hepatoma-derived growth factor (HDGF) mRNA, and the m6A reader IGF2BP3 then directly recognised and bound to the m6A site on HDGF mRNA and enhanced HDGF mRNA stability.

Hexokinase-2 (HK2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -2.06E+00 p-value: 3.79E-111
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.17E+00	GSE60213

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[54]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	Glycolysis / Gluconeogenesis	hsa00010
Cell Process	Glucose metabolism
Response Summary	METTL3 stabilizes Hexokinase-2 (HK2) and SLC2A1 (GLUT1) expression in colorectal cancer through an m6A-IGF2BP2/3- dependent mechanism.

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[55]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulation	Up regulation
Pathway Response	Glycolysis / Gluconeogenesis			hsa00010), Central carbon metabolism in cancer
Cell Process	Glycolysis
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	HT-3	Cervical carcinoma	Homo sapiens	CVCL_1293
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
In-vivo Model	Five-week-old male nude BALB/C mice were applied for this animal studies and fed with certified standard diet and tap water ad libitum in a light/dark cycle of 12 h on/12 h off.The assay was performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Stable transfection of METTL3 knockdown (sh-METTL3) or negative control (sh-blank) in SiHa cells (5 × 10⁶ cells per 0.1 mL) were injected into the flank of mice.
Response Summary	METTL3 enhanced the Hexokinase-2 (HK2) stability through YTHDF1-mediated m6A modification, thereby promoting the Warburg effect of CC, which promotes a novel insight for the CC treatment.

High mobility group protein HMGI-C (HMGA2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 4.44E+00 p-value: 5.85E-138
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.68E+00	GSE60213

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[56]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Pathway Response	Transcriptional misregulation in cancer			hsa05202
Cell Process	Epithelial-mesenchymal transition
	Cell autophagy
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
In-vivo Model	To create the xenograft neoplasm system, 40 male BALB/c nude mice aged 5 weeks were randomly separated into sh-NC, sh-circHPS5, sh-circHPS5+CTRL, and sh-circHPS5+SAH groups (n = 5 for each group). HCC cells were subcutaneously injected into the axilla of the nude mice.
Response Summary	In hepatocellular carcinoma, METTL3 could direct the formation of circHPS5, and specific m6A controlled the accumulation of circHPS5. YTHDC1 facilitated the cytoplasmic output of circHPS5 under m6A modification. CircHPS5 can act as a miR-370 sponge to regulate the expression of High mobility group protein HMGI-C (HMGA2) and further accelerate hepatocellular carcinoma cell tumorigenesis.

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[57]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
In-vivo Model	Eighteen BALB/C female nude mice aged 4-5 weeks and weighing 15-18 g were randomly assigned into three groups of six mice. The MCF-7 cell lines stably transfected with sh-NC + oe-NC, sh-METTL3 + oe-NC and sh-METTL3 + oe-HMGA2 were selected for subcutaneous establishment of the BC cell line MCF-7 as xenografts in the nude mice. For this purpose, MCF-7 cell lines in the logarithmic growth stage were prepared into a suspension with a concentration of about 1 × 10⁷ cells/ml. The prepared cell suspension was injected into the left armpit of the mice, and the subsequent tumor growth was recorded.
Response Summary	Silencing METTL3 down-regulate MALAT1 and High mobility group protein HMGI-C (HMGA2) by sponging miR-26b, and finally inhibit EMT, migration and invasion in BC, providing a theoretical basis for clinical treatment of BC.

Histone-lysine N-methyltransferase EZH2 (EZH2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -1.23E+00 p-value: 1.10E-12
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.01E+00	GSE60213

Nasopharyngeal carcinoma [ICD-11: 2B6B]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[58]
Responsed Disease	Nasopharyngeal carcinoma [ICD-11: 2B6B]
Target Regulation	Down regulation
Cell Process	Cell viability
In-vitro Model	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	C666-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_7949
	SUNE1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_6946
Response Summary	METTL3 was highly expressed in nasopharyngeal carcinoma tissues, which inhibited Histone-lysine N-methyltransferase EZH2 (EZH2) expression by mediating M6A modification of EZH2 mRNA.

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[59]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Response Summary	Simvastatin induces METTL3 down-regulation in lung cancer tissues, which further influences EMT via m6A modification on Histone-lysine N-methyltransferase EZH2 (EZH2) mRNA and thus inhibits the malignant progression of lung cancer.

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[60]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
Pathway Response	Adherens junction			hsa04520
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
Response Summary	METTL3 is upregulated in Breast Cancer. It could regulate the protein level of Histone-lysine N-methyltransferase EZH2 (EZH2) through m6A modification to promote EMT and metastasis in BCa cells, thereafter aggravating the progression of BCa.

Congenital pneumonia [ICD-11: KB24]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[61]
Responsed Disease	Congenital pneumonia [ICD-11: KB24]
Target Regulation	Up regulation
Pathway Response	JAK-STAT signaling pathway	hsa04630
Cell Process	Inflammation
In-vitro Model	HPBM (Human Peripheral Blood Monocytes)
Response Summary	METTL3 promotes inflammation and cell apoptosis in a pediatric pneumonia model by regulating Histone-lysine N-methyltransferase EZH2 (EZH2).

Homeobox protein Nkx-3.1 (NKX3-1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 1.12E+00 p-value: 7.44E-16
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 7.11E+00	GSE60213

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[62]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Down regulation
Pathway Response	Oxidative phosphorylation			hsa00190
In-vitro Model	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	RWPE-1	Normal	Homo sapiens	CVCL_3791
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
In-vivo Model	Approximately 2 × 10⁶ PCa cells (PC-3 shNC, shYTHDF2, shMETTL3 cell lines) per mouse suspended in 100 uL PBS were injected in the flank of male BALB/c nude mice (4 weeks old). During the 40-day observation, the tumor size (V = (width2×length ×0.52)) was measured with vernier caliper. Approximately 1.5 × 10⁶ PCa cells suspended in 100 uL of PBS (PC-3 shNC, shYTHDF2, and shMETTL3 cell lines) per mouse were injected into the tail vein of male BALB/c nude mice (4 weeks old). The IVIS Spectrum animal imaging system (PerkinElmer) was used to evaluate the tumor growth (40 days) and whole metastasis conditions (4 weeks and 6 weeks) with 100 uL XenoLight D-luciferin Potassium Salt (15 mg/ml, Perkin Elmer) per mouse. Mice were anesthetized and then sacrificed for tumors and metastases which were sent for further organ-localized imaging as above, IHC staining and hematoxylin-eosin (H&E) staining.
Response Summary	Knock-down of YTHDF2 or METTL3 significantly induced the expression of LHPP and Homeobox protein Nkx-3.1 (NKX3-1) at both mRNA and protein level with inhibited phosphorylated AKT. YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer.

Homeodomain-interacting protein kinase 2 (HIPK2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -1.67E+00 p-value: 2.62E-66
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.33E+00	GSE60213

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[22]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulation	Up regulation
Cell Process	Cell growth and death
	Cell apoptosis
In-vitro Model	ADR-resistant MCF-7 (MCF-7/ADR) cells (Human breast cancer doxorubicin-resistant cell line)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
In-vivo Model	Cell suspensions (2 × 10⁶ cells/mL) made with MCF-7/ADR cells stably expressing METTL3 and/or miR-221-3p inhibitor were subcutaneously implanted into each mouse. One week later, xenografted mice were injected with 0.1 mL ADR (25 mg/kg, intraperitoneal injection) twice a week.
Response Summary	METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating pri-microRNA-221-3p maturation in a m6A-dependent manner. METTL3 knockdown was shown to reduce the expression of miR-221-3p by reducing pri-miR-221-3p m6A mRNA methylation, reducing the expression of MDR1 and BCRP, and inducing apoptosis. Identified the METTL3/miR-221-3p/Homeodomain-interacting protein kinase 2 (HIPK2)/Che-1 axis as a novel signaling event that will be responsible for resistance of BC cells to ADR.

Insulin-like growth factor I (IGF1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	DKO-1 cell line	Homo sapiens
Treatment: METTL3 knockdown DKO-1 cell Control: DKO-1 cell		GSE182382
Regulation		logFC: -2.21E+00 p-value: 2.40E-02
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 6.27E+00	GSE60213

Ageing-related disease [ICD-11: 9B10-9B60]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[63]
Responsed Disease	Ageing-related disease [ICD-11: 9B10-9B60]
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair	hsa03420
Cell Process	DNA repair and mitochondrial stress
In-vitro Model	Mouse fibroblasts (Major cellular components of loose connective tissue)
Response Summary	The long-lived endocrine mutants - Snell dwarf, growth hormone receptor deletion and pregnancy-associated plasma protein-A knockout - all show increases in the N6-adenosine-methyltransferases (METTL3/14) that catalyze 6-methylation of adenosine (m6A) in the 5' UTR region of select mRNAs. In addition, these mice have elevated levels of YTHDF1, which recognizes m6A and promotes translation by a cap-independent mechanism. Augmented translation by cap-independent pathways facilitated by m6A modifications contribute to the stress resistance and increased healthy longevity of mice with diminished GH and Insulin-like growth factor I (IGF1) signals.

Integrin subunit beta 3 (ITGB3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -3.38E+00 p-value: 2.43E-215
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.57E+00	GSE60213

Nasopharyngeal carcinoma [ICD-11: 2B6B]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[64]
Responsed Disease	Nasopharyngeal carcinoma [ICD-11: 2B6B]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation and metastasis
In-vitro Model	5-8F	Nasopharyngeal carcinoma	Homo sapiens	CVCL_C528
	6-10B	Nasopharyngeal carcinoma	Homo sapiens	CVCL_C529
	C666-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_7949
	CNE-1	Normal	Homo sapiens	CVCL_6888
	CNE-2	Nasopharyngeal carcinoma	Homo sapiens	CVCL_6889
	HK1	Nasopharyngeal carcinoma	Acipenser baerii	CVCL_YE27
	HNE-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_0308
	HONE-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_8706
	N2Tert (The human immortalized nasopharyngeal epithelial cell lines)
	NP69 (A human immortalized nasopharyngeal epithelial)
	S18	Nasopharyngeal carcinoma	Homo sapiens	CVCL_B0U9
	S26	Nasopharyngeal carcinoma	Homo sapiens	CVCL_B0UB
	SUNE1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_6946
In-vivo Model	For the tumor growth model, 1 × 10⁶ HNE1-Scrambled or HNE1-shFAM2225A 2# cells were injected into the axilla of the mice, and the tumor size was measured every 3 days.
Response Summary	FAM225A functioned as a competing endogenous RNA (ceRNA) for sponging miR-590-3p and miR-1275, leading to the upregulation of their target Integrin subunit beta 3 (ITGB3), and the activation of FAK/PI3K/Akt signaling to promote Nasopharyngeal carcinoma cell proliferation and invasion. FAM225A showed lower RNA stability after silencing of METTL3.

Interstitial collagenase (MMP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -1.11E+00 p-value: 1.30E-35
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 8.91E+00	GSE60213

Osteoarthritis [ICD-11: FA05]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[33]
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulation	Up regulation
Cell Process	Inflammatory response
In-vitro Model	SW1353	Primary central chondrosarcoma	Homo sapiens	CVCL_0543
Response Summary	METTL3 is involved in OA probably by regulating the inflammatory response. METTL3 overexpression affects extracellular matrix degradation in OA by adjusting the balance between TIMPs and Interstitial collagenase (MMP1).

Kelch-like ECH-associated protein 1 (KEAP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HeLa cell line	Homo sapiens
Treatment: METTL3 knockdown HeLa cells Control: HeLa cells		GSE70061
Regulation		logFC: -1.79E+00 p-value: 1.23E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.17E+00	GSE60213

Diseases of the urinary system [ICD-11: GC2Z]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[65]
Responsed Disease	Diseases of the urinary system [ICD-11: GC2Z]
Responsed Drug	Colistin	Approved	Drug Info
Target Regulation	Down regulation
Cell Process	Oxidative stress
	Cell apoptosis
In-vivo Model	The 60 female Kunming mice were divided into two groups (n = 30): control group (injection of physiological saline through the caudal vein) and colistin group (injection of 15 mg/kg colistin, twice a day, with an eight-hour interval).
Response Summary	m6A methylation was involved in oxidative stress-mediated apoptosis in the mechanism of colistin nephrotoxicity. METTL3-mediated M6A methylation modification is involved in colistin-induced nephrotoxicity through apoptosis mediated by Kelch-like ECH-associated protein 1 (KEAP1)/Nrf2 signaling pathway.

Leukocyte surface antigen CD47 (CD47)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: 1.18E+00 p-value: 9.07E-25
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 4.98E+00	GSE60213

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[66]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
In-vitro Model	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
Response Summary	METTL3/IGF2BP1/Leukocyte surface antigen CD47 (CD47) mediated EMT transition contributes to the incomplete ablation induced metastasis in HCC cells.

MAP kinase signal-integrating kinase 2 (MNK2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 1.09E+00 p-value: 4.06E-29
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.25E+00	GSE60213

Muscular dystrophies [ICD-11: 8C70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[67]
Responsed Disease	Muscular dystrophies [ICD-11: 8C70]
Target Regulation	Up regulation
Pathway Response	MAPK signaling pathway			hsa04010
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vitro Model	C2C12	Normal	Mus musculus	CVCL_0188
In-vivo Model	For mouse muscle injury and regeneration experiment, tibialis anterior (TA) muscles of 6-week-old male mice were injected with 25 uL of 10 uM cardiotoxin (CTX, Merck Millipore, 217503), 0.9% normal saline (Saline) were used as control. The regenerated muscles were collected at day 1, 3, 5, and 10 post-injection. TA muscles were isolated for Hematoxylin and eosin staining or frozen in liquid nitrogen for RNA and protein extraction.
Response Summary	m6A writers METTL3/METTL14 and the m6A reader YTHDF1 orchestrate MAP kinase signal-integrating kinase 2 (MNK2) expression posttranscriptionally and thus control ERK signaling, which is required for the maintenance of muscle myogenesis and contributes to regeneration.

Metalloproteinase inhibitor 1 (TIMP-1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -1.77E+00 p-value: 2.62E-61
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.26E+00	GSE60213

Osteoarthritis [ICD-11: FA05]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[33]
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulation	Down regulation
Cell Process	Inflammatory response
In-vitro Model	SW1353	Primary central chondrosarcoma	Homo sapiens	CVCL_0543
Response Summary	METTL3 is involved in OA probably by regulating the inflammatory response. METTL3 overexpression affects extracellular matrix degradation in OA by adjusting the balance between Metalloproteinase inhibitor 1 (TIMP-1) and MMPs.

Metalloproteinase inhibitor 2 (TIMP2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 6.36E-01 p-value: 3.68E-18
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.22E+00	GSE60213

Osteoarthritis [ICD-11: FA05]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[33]
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulation	Down regulation
Cell Process	Inflammatory response
In-vitro Model	SW1353	Primary central chondrosarcoma	Homo sapiens	CVCL_0543
Response Summary	METTL3 is involved in OA probably by regulating the inflammatory response. METTL3 overexpression affects extracellular matrix degradation in OA by adjusting the balance between Metalloproteinase inhibitor 2 (TIMP2) and MMPs.

Chronic kidney disease [ICD-11: GB61]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[68]
Responsed Disease	Chronic kidney disease [ICD-11: GB61.Z]
Target Regulation	Up regulation
Pathway Response	Notch signaling pathway			hsa04330
In-vitro Model	MPC-5	Normal	Mus musculus	CVCL_AS87
In-vivo Model	After 7 days of acclimatization, STZ, dissolved in 0.1 M citrate buffer, was intraperitoneally administered daily to mice at a dose of 50 mg/kg after 12 h of food deprivation each day for 5 consecutive days. The type 1 mice diabetic mice were randomly separated into four groups (n = 5-8): AAV9-scramble-control group; AAV9-scramble-STZ; AAV9-shRNA-control; and AAV9-shRNA-STZ group (Hanbio Biotechnology, China). The 50 UL titer of 1 × 10¹² virus was injected into the renal pelvis using an insulin needle and maintained there for 2 to 3 s. The type 2 diabetic mice were randomly separated into four groups (n = 5-8): AAV9-scramble-db/m group; AAV9-scramble-db/db group; AAV9-shRNA-db/m group; and AAV9-shRNA-db/db group (Hanbio Biotechnology, China). The 100 UL titer of 1 × 10¹² virus was injected into the tail vein using an insulin needle and maintained there for 2 to 3 s. Blood glucose was monitored weekly in mice. At the end of 12 weeks, the 24-h urine samples were collected from the mice kept in metabolic cages.
Response Summary	METTL3 modulated Notch signaling via the m6A modification of Metalloproteinase inhibitor 2 (TIMP2) in IGF2BP2-dependent manner and exerted pro-inflammatory and pro-apoptotic effects. This study suggested that METTL3-mediated m6A modification is an important mechanism of podocyte injury in DN.

Methylated-DNA--protein-cysteine methyltransferase (MGMT)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -1.79E+00 p-value: 2.16E-20
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 5.15E+00	GSE60213

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[69]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Responsed Drug	Temozolomide		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	DNA repair
In-vitro Model	U251 (Fibroblasts or fibroblast like cells)
	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
In-vivo Model	Subcutaneously injected shMETTL3 or shNC-expressing U87-MG-TMZ cells into BALB/c NOD mice. After confirmation of GBM implantation, mice were treated with TMZ (66 mg/kg/d, 5 d per week, for 3 cycles).
Response Summary	Two critical DNA repair genes (Methylated-DNA--protein-cysteine methyltransferase (MGMT) and APNG) were m6A-modified by METTL3, whereas inhibited by METTL3 silencing or DAA-mediated total methylation inhibition, which is crucial for METTL3-improved temozolomide resistance in glioblastoma cells.

Methylcytosine dioxygenase TET1 (TET1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 1.21E+00 p-value: 3.76E-06
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 6.94E+00	GSE60213

Chronic pain [ICD-11: MG30]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[70]
Responsed Disease	Chronic pain [ICD-11: MG30]
Target Regulation	Down regulation
Response Summary	Downregulated spinal cord METTL3 coordinating with YTHDF2 contributes to the modulation of inflammatory pain through stabilizing upregulation of Methylcytosine dioxygenase TET1 (TET1) in spinal neurons.

Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B/LC3B-II)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 6.38E-01 p-value: 4.93E-09
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.34E+00	GSE60213

Enterovirus [ICD-11: 1A2Y]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[7]
Responsed Disease	Enterovirus [ICD-11: 1A2Y]
Target Regulation	Up regulation
Pathway Response	Autophagy	hsa04140
Cell Process	Cell proliferation and metastasis
	Cell apoptosis
	Cell autophagy
In-vitro Model	Schwann cells (A type of glial cell that surrounds neurons)
Response Summary	Knocking down METTL3 prevented Enterovirus 71-induced cell death and suppressed Enterovirus 71-induced expression of Bax while rescuing Bcl-2 expression after Enterovirus 71 infection. Knocking down METTL3 inhibited Enterovirus 71-induced expression of Atg5, Atg7 and Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B/LC3B-II). Knocking down METTL3 inhibited Enterovirus 71-induced apoptosis and autophagy.

Lung cancer [ICD-11: 2C25]

In total 3 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Chloroquine		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, ATG7, LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B/LC3B-II). beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Gefitinib		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, ATG7, LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B/LC3B-II). beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Experiment 3 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Beta-Elemen		Phase 3	Drug Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, ATG7, LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B/LC3B-II). beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.

Mitogen-activated protein kinase 14 (p38/MAPK14)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HeLa cell line	Homo sapiens
Treatment: METTL3 knockdown HeLa cells Control: HeLa cells		GSE70061
Regulation		logFC: -3.87E+00 p-value: 1.84E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.30E+00	GSE60213

Head and neck squamous carcinoma [ICD-11: 2B6E]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[71]
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulation	Up regulation
In-vitro Model	SCC-25	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1682
In-vitro Model	SCC-15	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1681
In-vivo Model	Male BALB/c-nu/nu mice, 9-10 weeks of age, were acclimatized for a week prior to the experiments. Nude mice (6 each group) were subcutaneously inoculated with 4 × 10⁶ SCC-25 or SCC-15 cells through an injection into the center of the back, which consistently caused tumor formation within 1 week of inoculation. To monitor the initial tumor appearance, animals were observed every day. After tumor appeared, measurements were made every week with a caliper. After 28 days, mice were sacrificed and tumors were dissected out to be weighed.
Response Summary	High METTL3 expression was positively correlated with more severe clinical features of OSCC tumors. Furthermore, METTL3-KD and cycloleucine, a methylation inhibitor, decreased m6A levels and down-regulated Mitogen-activated protein kinase 14 (p38/MAPK14) expression in OSCC cells.

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[72]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	KM12	Colon carcinoma	Homo sapiens	CVCL_1331
Response Summary	METTL3 played a tumor-suppressive role in Colorectal cancer cell proliferation, migration and invasion through Mitogen-activated protein kinase 14 (p38/MAPK14)/ERK pathways, which indicated that METTL3 was a novel marker for CRC carcinogenesis, progression and survival.

Mutated in multiple advanced cancers 1 (PTEN)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 9.60E-01 p-value: 1.46E-37
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.25E+00	GSE60213

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[9]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Up regulation
Cell Process	Cell differentiation and apoptosis
	Apoptosis (hsa04210)
In-vitro Model	HSPC (Human hematopoietic stem cell)
In-vivo Model	500,000 selected cells were injected via tail vein or retro-orbital route into female NSG (6-8 week old) recipient mice that had been sublethally irradiated with 475 cGy one day before transplantation.
Response Summary	METTL3 depletion in human myeloid leukemia cell lines induces cell differentiation and apoptosis and delays leukemia progression in recipient mice in vivo. Single-nucleotide-resolution mapping of m6A coupled with ribosome profiling reveals that m6A promotes the translation of c-MYC, BCL2 and Mutated in multiple advanced cancers 1 (PTEN) mRNAs in the human acute myeloid leukemia MOLM-13 cell line. Moreover, loss of METTL3 leads to increased levels of phosphorylated AKT.

Malignant haematopoietic neoplasm [ICD-11: 2B33]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[73]
Responsed Disease	Chronic myeloid leukaemia [ICD-11: 2B33.2]
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	RNA stability
	Cell autophagy
In-vitro Model	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	KCL-22	Chronic myelogenous leukemia	Homo sapiens	CVCL_2091
In-vivo Model	In the control mice or ADR mice group, the parental or chemo-resistant K562 cells were infected with LV-shCtrl. In the ADR + shLINC00470 group, the chemo-resistant K562 cells were infected with LV- shLINC00470. These cells were injected, respectively, into these 5-week-old mice subcutaneously.
Response Summary	The molecular mechanism underlying the effect of LINC00470 on chronic myelocytic leukaemia by reducing the Mutated in multiple advanced cancers 1 (PTEN) stability via RNA methyltransferase METTL3, thus leading to the inhibition of cell autophagy while promoting chemoresistance in CML.

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[74]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulation	Down regulation
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	Four-week-old BALB/c nude mice were randomly divided into three groups: (1) vector group, (2) vector + Bete-elemene group, and (3) Bete-elemene + METTL3 group. Nude mice were raised in an SPF level animal house and were free to eat and drink. Mice in the vector group were subcutaneously injected with lung cancer cells transfected with empty vector and did not receive Bete-elemene administration, and this group was implemented as the negative control. Following establishing orthotopic xenografts by using A549 or H1299 cells transfected with empty vector, mice in the vector + Bete-elemene group underwent intraperitoneal injection with Bete-elemene once a day. For the subcutaneous transplanted model, A549 or H1299 cells transfected with METTL3-overexpressing vector were inoculated into mice from the Bete-elemene + METTL3 group. Then, mice were intraperitoneally administrated with Bete-elemene once a day. Three weeks later, all the animals were euthanized with CO2. Xenografts were removed and weighted after mice were euthanatized.
Response Summary	Bete-elemene exerted the restrictive impacts on the cell growth of lung cancer in vivo and in vitro through targeting METTL3. Bete-elemene contributed to the augmented PTEN expression via suppressing its m6A modification.

Pulmonary hypertension [ICD-11: BB01]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[75]
Responsed Disease	Pulmonary hypertension due to lung disease or hypoxia [ICD-11: BB01.2]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway	hsa04151
Cell Process	Cell apoptosis
In-vitro Model	PASMC cell line (Pulmonary artery smooth muscle cell)
In-vivo Model	10 rats were divided into control and HPH group. In detail, 5 rats of the hypoxia groups were exposed to hypoxia (10%O₂) chamber (AiPu XBS-02B, China) for 4 weeks. In addition, 5 rats of control group were kept under normoxic conditions (21% O₂) for 4 weeks. Rats were housed in standard polypropylene cages under controlled photocycle (12 h light/12 h dark) under 22-25 ℃ temperature.
Response Summary	METTL3/YTHDF2/Mutated in multiple advanced cancers 1 (PTEN) axis exerts a significant role in hypoxia induced PASMCs proliferation, providing a novel therapeutic target for hypoxic pulmonary hypertension.

Myc proto-oncogene protein (MYC)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LNCaP cell line	Homo sapiens
Treatment: shMETTL3 LNCaP cells Control: shControl LNCaP cells		GSE147884
Regulation		logFC: -6.39E-01 p-value: 4.30E-103
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.10E+00	GSE60213

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[9]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Up regulation
Cell Process	Cell differentiation and apoptosis
	Apoptosis (hsa04210)
In-vitro Model	HSPC (Human hematopoietic stem cell)
In-vivo Model	500,000 selected cells were injected via tail vein or retro-orbital route into female NSG (6-8 week old) recipient mice that had been sublethally irradiated with 475 cGy one day before transplantation.
Response Summary	METTL3 depletion in human myeloid leukemia cell lines induces cell differentiation and apoptosis and delays leukemia progression in recipient mice in vivo. Single-nucleotide-resolution mapping of m6A coupled with ribosome profiling reveals that m6A promotes the translation of Myc proto-oncogene protein (MYC), BCL2 and PTEN mRNAs in the human acute myeloid leukemia MOLM-13 cell line. Moreover, loss of METTL3 leads to increased levels of phosphorylated AKT.

Head and neck squamous carcinoma [ICD-11: 2B6E]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[77]
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulation	Up regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	RNA stability
In-vitro Model	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107
	NHOK (Normal oral keratinocytes)
	SCC-15	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1681
	SCC-25	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1682
	TSCCa	Endocervical adenocarcinoma	Homo sapiens	CVCL_VL15
In-vivo Model	The stable transfection of SCC25 cells (1 × 10⁷ cells in 0.1 mL) with lenti-sh-METTL3 or blank vectors was injected subcutaneously into BALB/c nude mice.
Response Summary	In oral squamous cell carcinoma, YTH N6-methyladenosine RNA binding protein 1 (YTH domain family, member 1 [YTHDF1]) mediated the m6A-increased stability of Myc proto-oncogene protein (MYC) mRNA catalyzed by METTL3.

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[42]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	GES-1	Normal	Homo sapiens	CVCL_EQ22
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
	MKN74	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_2791
	pGCC (Primary GC cells)
	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
In-vivo Model	A total of 2 × 10⁶ GC cells were injected into the flank of nude mice in a 1:1 suspension of BD Matrigel (BD Biosciences) in phosphate-buffered saline (PBS) solution.
Response Summary	In gastric cancer, several component molecules (e.g., MCM5, MCM6, etc.) of Myc proto-oncogene protein (MYC) target genes were mediated by METTL3 via altered m6A modification.

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[79]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Cell Process	Cell proliferation
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	METTL3 stable knockdown or overexpression HCT116 cells were collected and resuspended at a density of 5 × 10⁶ or 3 × 10⁶ cells per 150 uL PBS.
Response Summary	METTL3 exerted its function through enhancing Myc proto-oncogene protein (MYC) expression, at least partially in an m6A-IGF2BP1-dependent manner. Knockdown of METTL3 suppressed colorectal cancer cell proliferation in vitro and in vivo.

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[47]
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulation	Up regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0608
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HOP-62	Lung adenocarcinoma	Homo sapiens	CVCL_1285
In-vivo Model	For the in vivo tumorigenicity assay, female BALB/c nude mice (ages 4-5 weeks) were randomly divided into two groups (n = 6/group). Calu1 cells (4 × 10⁶) that had been stably transfected with sh-LCAT3 or scramble were implanted subcutaneously into the nude mice. Tumor growth was measured after one week, and tumor volumes were calculated with the following formula: Volume (cm³) = (length × width²)/2. After four weeks, the mice were euthanized, and the tumors were collected and weighed. For the in vivo tumor invasion assay, 1.2 × 10⁶ scramble or shLCAT3 cells were injected intravenously into the tail vein of nude mice (n = 6/group). 1.5 mg luciferin (Gold Biotech, St Louis, MO, USA) was administered once a week for 4 weeks, to monitor metastases using an IVIS@ Lumina II system (Caliper Life Sciences, Hopkinton, MA, USA).
Response Summary	LCAT3 upregulation is attributable to N6-methyladenosine (m6A) modification mediated by methyltransferase like 3 (METTL3), leading to LCAT3 stabilization. LCAT3 as a novel oncogenic lncRNA in the lung, and validated the LCAT3-FUBP1-Myc proto-oncogene protein (MYC) axis as a potential therapeutic target for lung adenocarcinomas.

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[81]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	LNCaP C4-2	Prostate carcinoma	Homo sapiens	CVCL_4782
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
Response Summary	METTL3 enhanced Myc proto-oncogene protein (MYC) expression by increasing m6A levels of MYC mRNA transcript, leading to oncogenic functions in prostate cancer.

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[4]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Up regulation
Cell Process	Glucose metabolism
Response Summary	AF4/FMR2 family member 4 (AFF4), two key regulators of NF-Kappa-B pathway (IKBKB and RELA) and Myc proto-oncogene protein (MYC) were further identified as direct targets of METTL3-mediated m6A modification.overexpression of METTL3 significantly promoted Bladder cancer cell growth and invasion.

Polycystic kidney disease [ICD-11: GB81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[82]
Responsed Disease	Polycystic kidney disease [ICD-11: GB81]
Target Regulation	Up regulation
In-vitro Model	mIMCD-3	Normal	Mus musculus	CVCL_0429
In-vivo Model	The clone, with one wild-type Mettl3 allele and one L1L2_Bact_P cassette inserted allele, was injected into C57BL/6 blastocysts. Mettl3-targeted mouse line was established from a germline-transmitting chimera. The chimeric mouse was crossed to C57BL/6 Flp mice to excise the neomycin resistance system.
Response Summary	Mettl3 activates the cyst-promoting c-Myc and cAMP pathways through enhanced Myc proto-oncogene protein (MYC) and Avpr2 mRNA m6A modification and translation. Thus, Mettl3 promotes Autosomal dominant polycystic kidney disease and links methionine utilization to epitranscriptomic activation of proliferation and cyst growth.

Myeloid differentiation primary response protein MyD88 (MYD88)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shMETTL3 MOLM13 cells Control: MOLM13 cells		GSE98623
Regulation		logFC: -1.07E+00 p-value: 1.83E-13
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.16E+00	GSE60213

Pulpitis [ICD-11: DA09]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[83]
Responsed Disease	Pulpitis [ICD-11: DA09]
Target Regulation	Down regulation
Pathway Response	MAPK signaling pathway	hsa04010
Cell Process	Alternative splicing
Response Summary	Knocked down METTL3 and demonstrated that METTL3 depletion decreased the expression of inflammatory cytokines and the phosphorylation of IKK-alpha/beta, p65 and IKappa-B-alpha in the NF-Kappa-B signalling pathway as well as p38, ERK and JNK in the MAPK signalling pathway in LPS-induced HDPCs. METTL3 inhibits the LPS-induced inflammatory response of HDPCs by regulating alternative splicing of Myeloid differentiation primary response protein MyD88 (MYD88).

Skeletal anomaly [ICD-11: LD24]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[84]
Responsed Disease	Skeletal anomaly [ICD-11: LD24]
Target Regulation	Up regulation
Pathway Response	Central carbon metabolism in cancer	hsa05230
Cell Process	Glucose metabolism
In-vitro Model	Mesenchymal stem cell line (NP tissues were used to isolate NP cells)
Response Summary	METTL3 positively regulates expression of Myeloid differentiation primary response protein MyD88 (MYD88), a critical upstream regulator of NF-Kappa-B signaling, by facilitating m6A methylation modification to MYD88-RNA, subsequently inducing the activation of NF-Kappa-B which is widely regarded as a repressor of osteogenesis and therefore suppressing osteogenic progression. The METTL3-mediated m6A methylation is found to be dynamically reversed by the demethylase ALKBH5.

NACHT, LRR and PYD domains-containing protein 3 (NLRP3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 8.32E-01 p-value: 1.76E-06
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 7.81E+00	GSE60213

Atherosclerosis [ICD-11: BD40]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[85]
Responsed Disease	Atherosclerosis [ICD-11: BD40.Z]
Target Regulation	Up regulation
In-vitro Model	MAEC	Normal	Mus musculus	CVCL_U411
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
Response Summary	In the in vivo atherosclerosis model,partial ligation of the carotid artery led to plaque formation and up-regulation of METTL3 and NLRP1, with down-regulation of KLF4; knockdown of METTL3 via repetitive shRNA administration prevented the atherogenic process, NACHT, LRR and PYD domains-containing protein 3 (NLRP3) up-regulation, and KLF4 down-regulation. Collectively, it has demonstrated that METTL3 serves a central role in the atherogenesis induced by oscillatory stress and disturbed blood flow.

Chronic kidney disease [ICD-11: GB61]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[86]
Responsed Disease	Chronic kidney disease [ICD-11: GB61.Z]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	MPC-5	Normal	Mus musculus	CVCL_AS87
Response Summary	TFA could ameliorate HG-induced pyroptosis and injury in podocytes by targeting METTL3-dependent m6A modification via the regulation of NACHT, LRR and PYD domains-containing protein 3 (NLRP3)-inflammasome activation and PTEN/PI3K/Akt signaling. This study provides a better understanding of how TFA can protect podocytes in diabetic kidney disease (DKD).

Neuroblast differentiation-associated protein AHNAK (AHNAK)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shMETTL3 MOLM13 cells Control: MOLM13 cells		GSE98623
Regulation		logFC: 1.10E+00 p-value: 5.50E-75
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.20E+00	GSE60213

Corneal injury [ICD-11: NA06]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[87]
Responsed Disease	Corneal injury [ICD-11: NA06.4]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
In-vitro Model	CGC (Conjunctival goblet cells)
In-vivo Model	Mettl3^fl/wt mice were generated as previously described. Mettl3^fl/wt mice were crossed with K14CreER mice to obtain K14^creER/Mettl3^fl/fl (cKO) mice. Mettl3 cKO and control mice were injected with tamoxifen and then were subjected to corneal alkali burn treatment. The right eye was the experimental eye, and the left eye was the control eye. The mice were sacrificed at 24 hours, 7 days, 14 days, 35 days, and 56 days after injury. Six mice were taken from each period. Both eyes were removed, frozen in OCT (n = 4), fixed in 4% paraformaldehyde, and embedded in conventional paraffin (n = 2).
Response Summary	METTL3 knockout in the limbal stem cells promotes the in vivo cell proliferation and migration, leading to the fast repair of corneal injury. In addition, m6A modification profiling identified stem cell regulatory factors Neuroblast differentiation-associated protein AHNAK (AHNAK) and DDIT4 as m6A targets.

Neurocalcin-delta (NCALD)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LNCaP cell line	Homo sapiens
Treatment: shMETTL3 LNCaP cells Control: shControl LNCaP cells		GSE147884
Regulation		logFC: 1.15E+00 p-value: 3.16E-04
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 8.03E+00	GSE60213

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[88]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Fluorouracil		Approved	Drug Info
Target Regulation	Down regulation
In-vitro Model	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vivo Model	A tumor-bearing model was established by subcutaneously injecting 100 ul HT29 cells (5×10⁶) followed by an intravenous injection of CAFs-derived exosomes (50 ug/mouse every three days) into the tail vein of the mice. An intraperitoneal injection of 5-FU (50 mg/kg, every week) was administered on day 12.
Response Summary	METTL3?dependent m6A methylation was upregulated in CRC to promote the processing of miR?181d?5p by DGCR8. This led to increased miR?181d?5p expression, which inhibited the 5?FU sensitivity of CRC cells by targeting Neurocalcin-delta (NCALD).

Nuclear receptor-interacting protein 1 (NRIP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	DKO-1 cell line	Homo sapiens
Treatment: METTL3 knockdown DKO-1 cell Control: DKO-1 cell		GSE182382
Regulation		logFC: -1.29E+00 p-value: 1.52E-02
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.30E+00	GSE60213

Down syndrome [ICD-11: LD40]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[89]
Responsed Disease	Complete trisomy 21 [ICD-11: LD40.0]
Target Regulation	Down regulation
In-vitro Model	HT22	Normal	Mus musculus	CVCL_0321
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	The NRIP1 mRNA increased in fetal brain tissues of DS, whereas the m6A modification of the NRIP1 mRNA significantly decreased. METTL3 knockdown reduced the m6A modification of NRIP1 mRNA and increased its expression, and an increase in NRIP1 m6A modification and a decrease in its expression were observed in METTL3-overexpressed cells.

Parathyroid hormone 1 receptor (PTH1R)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -1.67E+00 p-value: 4.51E-08
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 6.67E+00	GSE60213

Low bone mass disorder [ICD-11: FB83]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[90]
Responsed Disease	Osteoporosis [ICD-11: FB83.1]
Target Regulation	Up regulation
Pathway Response	Parathyroid hormone synthesis, secretion and action	hsa04928
Cell Process	Adipogenesis
In-vivo Model	Mettl3^fl/+ mice with C57BL6/J background were generated using CRISPR-Cas9 systems.
Response Summary	Knockout of Mettl3 reduces the translation efficiency of MSCs lineage allocator Parathyroid hormone 1 receptor (PTH1R), and disrupts the PTH-induced osteogenic and adipogenic responses in vivo.

Paternally-expressed gene 3 protein (PEG3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LNCaP cell line	Homo sapiens
Treatment: shMETTL3 LNCaP cells Control: shControl LNCaP cells		GSE147884
Regulation		logFC: -6.51E-01 p-value: 1.16E-264
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 5.95E+00	GSE60213

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[91]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	The 40 nude mice of each large group were classified into 8 small groups (n = 5) and subcutaneously injected with transfected cell suspension in the back (5 × 10⁶ cells/mL/mouse). The length and width of tumors were recorded every 4 days, and the tumor volume = (length × width²)/2. The tumor growth curve was thereby graphed. On the 28^th day of injection, mice were euthanized by neck dislocation, and the xenografts were harvested, photographed, and weighed
Response Summary	METTL3 regulates the m6A modification to promote the maturation of miR-1246, which targets Paternally-expressed gene 3 protein (PEG3) to participate in occurrence and development of non-small cell lung cancer.

Peroxisomal bifunctional enzyme (EHHADH)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -7.43E-01 p-value: 3.92E-35
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 7.66E+00	GSE60213

Type 2 diabetes mellitus [ICD-11: 5A11]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[48]
Responsed Disease	Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulation	Up regulation
Pathway Response	Insulin resistance			hsa04931
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3^fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3^fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3^fl/fl) were used for experiments.
Response Summary	Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. The expression of Acc1, Acly, Dgat2, Peroxisomal bifunctional enzyme (EHHADH), Fasn, Foxo, Pgc1a and Sirt1, which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.

Peroxisome proliferator-activated receptor alpha (PPARalpha/PPARA)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -3.42E+00 p-value: 1.41E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 8.50E+00	GSE60213

Metabolic disorders [ICD-11: 5D2Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[92]
Responsed Disease	Metabolic disorders [ICD-11: 5D2Z]
Target Regulation	Down regulation
Pathway Response	PPAR signaling pathway			hsa03320
	Adipocytokine signaling pathway			hsa04920
Cell Process	Llipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hepa 1-6	Hepatocellular carcinoma of the mouse	Mus musculus	CVCL_0327
In-vivo Model	Liver-specific Bmal1^f/f-AlbCre-knockout mice were purchased from Jackson Laboratory. C57BI/6J or Bmal1^f/f-AlbCre-knockout male mice were maintained under a 12 hr light/12 hr dark (LD) cycle (ZT0 = 6 AM) and fed ad libitum with normal rodent chow (2018 Global 18% Protein diet, Envigo) and water. At 10-14 weeks of age, 10 male mice per group were sacrificed via CO2 asphyxiation at Zeitgeber Time (ZT) 0,2,6,10,12,14,18,22. In order to induce high levels of ROS in the liver, WT male mice were fasted 12 h and followed by intraperitoneal injection with 300 mg/kg APAP dissolved in PBS and re-fed.
Response Summary	PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Hepatic deletion of Bmal1 increases m6A mRNA methylation, particularly of Peroxisome proliferator-activated receptor alpha (PPARalpha/PPARA). Inhibition of m6A methylation via knockdown of m6A methyltransferase METTL3 decreases PPaR-Alpha m6A abundance and increases PPaRalpha mRNA lifetime and expression, reducing lipid accumulation in cells in vitro. YTHDF2 binds to PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Transcriptional regulation of circadian rhythms is essential for lipid metabolic homeostasis, disruptions of which can lead to metabolic diseases.

Pescadillo homolog (PES1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HeLa cell line	Homo sapiens
Treatment: METTL3 knockdown HeLa cells Control: HeLa cells		GSE70061
Regulation		logFC: 7.23E-01 p-value: 7.36E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.38E+00	GSE60213

Malignant haematopoietic neoplasm [ICD-11: 2B33]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[93]
Responsed Disease	Chronic myeloid leukaemia [ICD-11: 2B33.2]
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Decrease of S phase
In-vitro Model	U-937	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	LAMA-84	Chronic myelogenous leukemia	Homo sapiens	CVCL_0388
	KCL-22	Chronic myelogenous leukemia	Homo sapiens	CVCL_2091
	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	HL-60	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	HEL	Erythroleukemia	Homo sapiens	CVCL_0001
Response Summary	m6A methyltransferase complex METTL3/METTL14 is upregulated in CML patients and that is required for proliferation of primary CML cells and CML cell lines sensitive and resistant to the TKI imatinib. METTL3 directly regulates the level of Pescadillo homolog (PES1) protein identified as an oncogene in several tumors. These results point to METTL3 as a novel relevant oncogene in CML and as a promising therapeutic target for TKI resistant CML.

PHLPP-like (PHLPP2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: METTL3 knockdown MDA-MB-231 cells Control: MDA-MB-231 cells		GSE70061
Regulation		logFC: 7.59E-01 p-value: 9.18E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.40E+00	GSE60213

Endometrial cancer [ICD-11: 2C76]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[94]
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation and tumorigenicity
In-vitro Model	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293
	RL95-2	Endometrial adenosquamous carcinoma	Homo sapiens	CVCL_0505
	T HESCs	Normal	Homo sapiens	CVCL_C464
In-vivo Model	4×10⁶ HEC-1-A endometrial cancer cells (shCtrl, shMETTL3, wild-type, METTL14^+/-, or METTL14^+/- rescued with wild-type or mutant METTL14) were injected intraperitoneally into 5 week old female athymic nude mice (Foxn1^nu, Harlan; n=10 per group).
Response Summary	About 70% of endometrial tumours exhibit reductions in m6A methylation that are probably due to either this METTL14 mutation or reduced expression of METTL3. Reductions in m6A methylation lead to decreased expression of the negative AKT regulator PHLPP-like (PHLPP2) and increased expression of the positive AKT regulator mTORC2. these results reveal reduced m6A mRNA methylation as an oncogenic mechanism in endometrial cancer and identify m6A methylation as a regulator of AKT signalling.

Phosphatidylinositol 3-kinase regulatory subunit beta (PI3K-p85/PIK3R2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 1.59E+00 p-value: 3.69E-27
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.42E+00	GSE60213

Retina cancer [ICD-11: 2D02]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[44]
Responsed Disease	Retinoblastoma [ICD-11: 2D02.2]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
	mTOR signaling pathway			hsa04150
	Apoptosis			hsa04210
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	WERI-Rb-1	Retinoblastoma	Homo sapiens	CVCL_1792
	Y-79	Retinoblastoma	Homo sapiens	CVCL_1893
In-vivo Model	To establish a subcutaneous tumour model in nude mice, 2 × 10⁷ Y79 cells (METTL3 knockdown group: shNC, shRNA1 and shRNA2; METTL3 up-regulated group: NC and METLL3) were resuspended in 1 mL of pre-cooled PBS, and 200 uL of the cell suspension was injected subcutaneously into the left side of the armpit to investigate tumour growth (4 × 10⁶ per mouse).
Response Summary	METTL3 promotes the progression of retinoblastoma through Phosphatidylinositol 3-kinase regulatory subunit beta (PI3K-p85/PIK3R2)/AKT/mTOR pathways in vitro and in vivo. METTL3 has an impact on the PI3K-AKT-mTOR-P70S6K/4EBP1 pathway. The cell proliferation results show that the stimulatory function of METTL3 is lost after rapamycin treatment.

Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -1.51E+00 p-value: 1.12E-09
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 8.41E+00	GSE60213

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[62]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Down regulation
Pathway Response	Oxidative phosphorylation			hsa00190
In-vitro Model	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	RWPE-1	Normal	Homo sapiens	CVCL_3791
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
In-vivo Model	Approximately 2 × 10⁶ PCa cells (PC-3 shNC, shYTHDF2, shMETTL3 cell lines) per mouse suspended in 100 uL PBS were injected in the flank of male BALB/c nude mice (4 weeks old). During the 40-day observation, the tumor size (V = (width2×length ×0.52)) was measured with vernier caliper. Approximately 1.5 × 10⁶ PCa cells suspended in 100 uL of PBS (PC-3 shNC, shYTHDF2, and shMETTL3 cell lines) per mouse were injected into the tail vein of male BALB/c nude mice (4 weeks old). The IVIS Spectrum animal imaging system (PerkinElmer) was used to evaluate the tumor growth (40 days) and whole metastasis conditions (4 weeks and 6 weeks) with 100 uL XenoLight D-luciferin Potassium Salt (15 mg/ml, Perkin Elmer) per mouse. Mice were anesthetized and then sacrificed for tumors and metastases which were sent for further organ-localized imaging as above, IHC staining and hematoxylin-eosin (H&E) staining.
Response Summary	Knock-down of YTHDF2 or METTL3 significantly induced the expression of Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) and NKX3-1 at both mRNA and protein level with inhibited phosphorylated AKT. YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer.

Pigment epithelium-derived factor (PEDF)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -9.30E-01 p-value: 1.13E-16
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 8.75E+00	GSE60213

Diffuse large B-cell lymphomas [ICD-11: 2A81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[95]
Responsed Disease	Diffuse large B-cell lymphomas [ICD-11: 2A81]
Target Regulation	Up regulation
In-vitro Model	U-2932	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_1896
	SU-DHL-4	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_0539
	OCI-Ly10	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_8795
	HBL-1 [Human diffuse large B-cell lymphoma]	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_4213
	GM12878	Human B lymphocytes	Homo sapiens	CVCL_7526
	Farage	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_3302
Response Summary	Overexpressed Pigment epithelium-derived factor (PEDF) abrogates the inhibition of cell proliferation in DLBCL cells that is caused by METTL3 silence.

Platelet-derived growth factor receptor alpha (PDGFRA)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 1.93E+00 p-value: 8.84E-11
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 4.83E+00	GSE60213

Diseases of arteries or arterioles [ICD-11: BD5Y]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[96]
Responsed Disease	Diseases of arteries or arterioles [ICD-11: BD5Y]
Target Regulation	Down regulation
In-vitro Model	ACBRI-183 (Human retinal pericytes (ACBRI-183) was obtained from Cell Systems Corp. (CSC, USA))
In-vivo Model	Mettl3 floxed mice were purchased from GemPharmatech Co. Ltd (Nanjing, China). Pdgfr-Beta-Cre mice were purchased from Beijing Biocytogen Co. Ltd (Beijing, China) generated on C57BL/6J background. Mettl3 ^flox/flox mice were crossed with Pdgfr-Beta-Cre mice to generate pericyte-specific Mettl3 knockout mice. All mice were bred under the specific-pathogen free condition with free access to diet and water or their nursing mothers with alternating 12/12 light-dark cycle (lights on at 08:00 and off at 20:00).
Response Summary	Specific depletion of METTL3 in pericytes suppressed diabetes-induced pericyte dysfunction and Microvascular complication in vivo. METTL3 overexpression impaired pericyte function by repressing PKC-Eta, FAT4, and Platelet-derived growth factor receptor alpha (PDGFRA) expression, which was mediated by YTHDF2-dependent mRNA decay.

Poly [ADP-ribose] polymerase tankyrase-1 (Tankyrase)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Pancreatic islets	Mus musculus
Treatment: Mettl3 knockout mice Control: Mettl3 flox/flox mice		GSE155612
Regulation		logFC: 8.10E-01 p-value: 1.68E-04
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.44E+00	GSE60213

Nasopharyngeal carcinoma [ICD-11: 2B6B]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[24]
Responsed Disease	Nasopharyngeal carcinoma [ICD-11: 2B6B]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	Neural progenitor cells (NPCs) (The progenitor cells of the CNS)
	NP69 (A human immortalized nasopharyngeal epithelial)
	HNE-2	Nasopharyngeal carcinoma	Homo sapiens	CVCL_FA07
	HNE-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_0308
	CNE-2	Nasopharyngeal carcinoma	Homo sapiens	CVCL_6889
	CNE-1	Normal	Homo sapiens	CVCL_6888
In-vivo Model	1 × 10⁵ HNE2 cells (with or without METTL3 knockdown) were labeled with luciferase gene and injected into the tail vein of the nude mice.
Response Summary	METTL3 activated the luciferase activity of TOPflash (a reporter for beta-catenin/TCF signaling), and downregulation of METTL3 inhibited the expression of beta-catenin/TCF target genes vimentin and N-cadherin, which are two regulators of epithelial-mesenchymal transition. METTL3 silencing decreased the m6A methylation and total mRNA levels of Poly [ADP-ribose] polymerase tankyrase-1 (Tankyrase), a negative regulator of axin. METTL3 is a therapeutic target for NPC.

Potassium voltage-gated channel subfamily H member 6 (KCNH6)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Embryonic stem cells	Mus musculus
Treatment: METTL3 knockout mESCs Control: Wild type mESCs		GSE156481
Regulation		logFC: 1.67E+00 p-value: 2.01E-04
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 4.49E+00	GSE60213

Idiopathic interstitial pneumonitis [ICD-11: CB03]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[97]
Responsed Disease	Idiopathic pulmonary fibrosis [ICD-11: CB03.4]
Target Regulation	Up regulation
In-vitro Model	WI-38	Normal	Homo sapiens	CVCL_0579
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Animals were bred and housed in the pathogen-free facility of the Laboratory Animal Center of Shanghai General Hospital (Shanghai, China). All lungs were collected 4 weeks after BLM treatment for histology and further study. Lung microsections (5 uM) were applied to Masson's trichrome and Sirius red staining to visualize fibrotic lesions.
Response Summary	Lowering m6A levels through silencing METTL3 suppresses the FMT process in vitro and in vivo. m6A modification regulates EMT by modulating the translation of Potassium voltage-gated channel subfamily H member 6 (KCNH6) mRNA in a YTHDF1-dependent manner. Manipulation of m6A modification through targeting METTL3 becomes a promising strategy for the treatment of idiopathic pulmonary fibrosis.

Pro-epidermal growth factor (EGF)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HeLa cell line	Homo sapiens
Treatment: METTL3 knockdown HeLa cells Control: HeLa cells		GSE70061
Regulation		logFC: 2.08E+00 p-value: 3.08E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 7.98E+00	GSE60213

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[98]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Homologous recombination			hsa03440
Cell Process	Homologous recombination repair
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
In-vivo Model	Cells were trypsinized and resuspended in DMEM at a consistence of 1 × 10⁷ cells/ml. A total of 1 × 106 cells were injected into flank of mice. 27 days after injection, tumors were removed for paraffin-embedded sections.
Response Summary	Knockdown of METTL3 sensitized these breast cancer cells to Adriamycin (ADR; also named as doxorubicin) treatment and increased accumulation of DNA damage. Mechanically, we demonstrated that inhibition of METTL3 impaired HR efficiency and increased ADR-induced DNA damage by regulating m6A modification of Pro-epidermal growth factor (EGF)/RAD51 axis. METTL3 promoted EGF expression through m6A modification, which further upregulated RAD51 expression, resulting in enhanced HR activity.

Programmed cell death 1 ligand 1 (CD274/PD-L1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -1.82E+00 p-value: 4.68E-65
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 7.97E+00	GSE60213

Head and neck squamous carcinoma [ICD-11: 2B6E]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[99]
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
In-vitro Model	SCC-9	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1685
	SCC-4	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1684
	SCC-25	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1682
	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107
In-vivo Model	Six-week-old nude mice were randomly divided into two groups (three mice per group) and cultured with continuous access to sterile food and water in pathogen-free sterile conditions. To establish the OSCC xenograft model, we subcutaneously injected 5 × 10⁶ SCC-9 cells stably transfected with METTL3 shRNA or sh-NC vectors into nude mice.
Response Summary	METTL3 intensified the metastasis and proliferation of OSCC by modulating the m6A amounts of PRMT5 and Programmed cell death 1 ligand 1 (CD274/PD-L1).

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[80]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Pathway Response	p53 signaling pathway	hsa04115
	Central carbon metabolism in cancer	hsa05230
	PD-L1 expression and PD-1 checkpoint pathway in cancer	hsa05235
Response Summary	This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher Programmed cell death 1 ligand 1 (CD274/PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, E2 transcription Factor (E2F) targets were significantly enriched.

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[100]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Tumor immune escape
In-vitro Model	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-10A	Normal	Homo sapiens	CVCL_0598
	HCC38	Breast ductal carcinoma	Homo sapiens	CVCL_1267
	4T1	Normal	Mus musculus	CVCL_0125
In-vivo Model	For subcutaneous xenograft experiments in B-NDG mice, approximately 1 × 10⁶ MDA-MB-231 and there was subcutaneous injection of the cells that resuspended in 100 uL PBS into the left flank of the mice and were divided into 11 groups randomly (each containing 5 mice). After the treatment Atezolizumab (Selleck, Shanghai, China) or corresponding iso control antibody (Selleck, Shanghai, China) was injected intratumorally on day 3, 6, 9, 12, 15 post-MDA-MB-231 inoculations, and 5 × 10⁶ cytokine-induced killer (CIK) cells were injected in the tail vein on day 7, 14, 21.
Response Summary	Programmed cell death 1 ligand 1 (CD274/PD-L1) was a downstream target of METTL3-mediated m6A modification in breast cancer cells. METTL3-mediated PD-L1 mRNA activation was m6A-IGF2BP3-dependent. PD-L1 expression was also positively correlated with METTL3 and IGF2BP3 expression in breast cancer tissues.

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[101]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
In-vitro Model	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	J82	Bladder carcinoma	Homo sapiens	CVCL_0359
	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
In-vivo Model	male C57BL/6J mice (6 weeks old) were given drinking water containing 0.05% (w/v) BBN (TCI, catalog no. B0938) for 20 weeks. After the BBN administration, mice were given normal drinking water and injected with 10% DMSO (as a control) or 20 mg/kg SP600125 (Selleck, catalog no. 129-56-6) i.p. every 3 days. After seven injections, mice were euthanized for tissue retrieval. For the bladder cancer cell-derived xenograft mouse model, male C57BL/6J mice (6 weeks old) were injected subcutaneously with 1 × 10⁶ MB49 cells. One week after bladder cancer cell injection, 10% DMSO or 20 mg/kg SP600125 were injected i.p. every 3 days.
Response Summary	METTL3 was essential for bladder cancer cells to resist the cytotoxicity of CD8+ T cells by regulating Programmed cell death 1 ligand 1 (CD274/PD-L1) expression. Additionally, JNK signaling contributed to tumor immune escape in a METTL3-dependent manner both in vitro and in vivo.

Protein arginine N-methyltransferase 5 (PRMT5)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Pancreatic islets	Mus musculus
Treatment: Mettl3 knockout mice Control: Mettl3 flox/flox mice		GSE155612
Regulation		logFC: 7.02E-01 p-value: 6.96E-04
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 5.94E+00	GSE60213

Head and neck squamous carcinoma [ICD-11: 2B6E]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[99]
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
In-vitro Model	SCC-9	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1685
	SCC-4	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1684
	SCC-25	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1682
	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107
In-vivo Model	Six-week-old nude mice were randomly divided into two groups (three mice per group) and cultured with continuous access to sterile food and water in pathogen-free sterile conditions. To establish the OSCC xenograft model, we subcutaneously injected 5 × 10⁶ SCC-9 cells stably transfected with METTL3 shRNA or sh-NC vectors into nude mice.
Response Summary	METTL3 intensified the metastasis and proliferation of OSCC by modulating the m6A amounts of Protein arginine N-methyltransferase 5 (PRMT5) and PD-L1.

Protein SET (SET)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HeLa cell line	Homo sapiens
Treatment: METTL3 knockdown HeLa cells Control: HeLa cells		GSE70061
Regulation		logFC: 5.30E+00 p-value: 1.65E-04
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.53E+00	GSE60213

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[102]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Down regulation
Pathway Response	TNF signaling pathway			hsa04668
Cell Process	Cell migration
	Cell invasion
	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Response Summary	miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor KLF4. miR-1915-3p function as a tumor suppressor by targeting Protein SET (SET) and has an anti-metastatic therapeutic potential for lung cancer treatment.

Proto-oncogene c-Rel (c-Rel)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Pancreatic islets	Mus musculus
Treatment: Mettl3 knockout mice Control: Mettl3 flox/flox mice		GSE155612
Regulation		logFC: 1.39E+00 p-value: 2.50E-05
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.02E+00	GSE60213

Thyroid Cancer [ICD-11: 2D10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[103]
Responsed Disease	Papillary thyroid cancer [ICD-11: 2D10.1]
Target Regulation	Down regulation
Pathway Response	NF-kappa B signaling pathway			hsa04064
In-vitro Model	TPC-1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
	Nthy-ori 3-1	Normal	Homo sapiens	CVCL_2659
	KTC-1	Thyroid carcinoma	Homo sapiens	CVCL_6300
	B-CPAP	Thyroid gland carcinoma	Homo sapiens	CVCL_0153
In-vivo Model	For xenograft models, 5 × 10⁶ BCPAP or KTC-1 cells from each group were injected subcutaneously into the flanks of female BALB/c nude mice (4-6 weeks old, Shanghai SLAC Laboratory Animal, China, n = 5 per group) in a volume of 150 uL PBS. Tumor growth was measured with a digital caliper every 4 days and calculated using the following formula: (length × width2)/2. To study the effect of IL-8 on tumor growth in vivo, scramble or shMETTL3 BCPAP cells were implanted hypodermically into BALB/c nude mice (2 × 10⁶ cells in 150 uL PBS, n = 10 per group). When palpable tumors formed on day 14, mice were treated with DMSO or the IL-8 inhibitor SB225002 (10 mg/kg) by intraperitoneal injection 3 times per week for 3 weeks. Six weeks post-injection, the mice were sacrificed, and the tumors were collected to analyze the frequency of TANs by flow cytometry. For the lung metastasis model, BCPAP and KTC-1 cells (2 × 10⁶ cells in 100 uL PBS) with the corresponding vectors were injected into the tail veins of BALB/c nude mice. Eight weeks after injection, the mice were euthanized, and metastatic lung nodules were analyzed (n = 5 for each group).
Response Summary	METTL3 played a pivotal tumor-suppressor role in papillary thyroid cancer carcinogenesis through Proto-oncogene c-Rel (c-Rel) and RelA inactivation of the nuclear factor Kappa-B (NF-Kappa-B) pathway by cooperating with YTHDF2 and altered TAN infiltration to regulate tumor growth

Pyruvate dehydrogenase kinase isoform 4 (PDK4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -1.03E+01 p-value: 3.59E-12
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 5.02E+00	GSE60213

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[104]
Responsed Disease	Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Target Regulation	Up regulation
Pathway Response	Glycerolipid metabolism			hsa00561
Cell Process	Glycolysis
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
In-vivo Model	As to the subcutaneous transplanted model, WT^Vec, Mettl3^Mut/-+vec, WTPDK4, Mettl3^Mut/-+vecPDK4 cells (2 × 10⁶ per mouse, n = 10 for each group) were diluted in 200 uL normal medium + 200 uL Matrigel (BD Biosciences) and subcutaneously injected into immunodeficient mice to investigate tumor growth.
Response Summary	m6A regulates glycolysis of cancer cells through Pyruvate dehydrogenase kinase isoform 4 (PDK4). Knockdown of Mettl3 significantly attenuated m6A antibody enriched PDK4 mRNA in Huh7 cells. It reveals that m6A regulates glycolysis of cancer cells through PDK4.

Ribosomal protein S6 kinase beta-1 (RPS6KB1/p70S6K)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	CT26 cell line	Mus musculus
Treatment: METTL3 knockout CT26 cells Control: CT26 cells		GSE142589
Regulation		logFC: -6.86E-01 p-value: 2.67E-02
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.70E+00	GSE60213

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
Response Summary	Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors Ribosomal protein S6 kinase beta-1 (RPS6KB1/p70S6K) and Cyclin D1.

Retina cancer [ICD-11: 2D02]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[44]
Responsed Disease	Retinoblastoma [ICD-11: 2D02.2]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
	mTOR signaling pathway			hsa04150
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	WERI-Rb-1	Retinoblastoma	Homo sapiens	CVCL_1792
	Y-79	Retinoblastoma	Homo sapiens	CVCL_1893
In-vivo Model	To establish a subcutaneous tumour model in nude mice, 2 × 10⁷ Y79 cells (METTL3 knockdown group: shNC, shRNA1 and shRNA2; METTL3 up-regulated group: NC and METLL3) were resuspended in 1 mL of pre-cooled PBS, and 200 uL of the cell suspension was injected subcutaneously into the left side of the armpit to investigate tumour growth (4 × 10⁶ per mouse).
Response Summary	METTL3 promotes the progression of retinoblastoma through PI3K/AKT/mTOR pathways in vitro and in vivo. METTL3 has an impact on the PI3K-AKT-mTOR-Ribosomal protein S6 kinase beta-1 (RPS6KB1/p70S6K)/4EBP1 pathway. The cell proliferation results show that the stimulatory function of METTL3 is lost after rapamycin treatment.

RIG-I-like receptor 1 (RIG-I)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -1.14E+00 p-value: 3.48E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.75E+00	GSE60213

Acute viral hepatitis [ICD-11: 1E50]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[105]
Responsed Disease	Acute hepatitis B [ICD-11: 1E50.1]
Target Regulation	Down regulation
Pathway Response	RIG-I-like receptor signaling pathway			hsa04622
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
Response Summary	METTL3 and METTL14 leads to an increase in viral RNA recognition by RIG-I-like receptor 1 (RIG-I), thereby stimulating type I interferon production. The obvious advantage is that m6A deficiency in HBV and HCV induces a higher IFN synthesis and in turn enhance adaptive immunity.

COVID-19 [ICD-11: RA01]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[106]
Responsed Disease	COVID-19 [ICD-11: RA01]
Target Regulation	Down regulation
Pathway Response	RIG-I-like receptor signaling pathway			hsa04622
Cell Process	Immune responses
In-vitro Model	Calu-3	Lung adenocarcinoma	Homo sapiens	CVCL_0609
	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	HEK293-FT	Normal	Homo sapiens	CVCL_6911
Response Summary	In SARS-CoV-2 infection, depletion of the host cell m6A methyltransferase METTL3 decreases m6A levels in SARS-CoV-2 and host genes, and m6A reduction in viral RNA increases RIG-I-like receptor 1 (RIG-I) binding and subsequently enhances the downstream innate immune signaling pathway and inflammatory gene expression.

Sequestosome-1 (SQSTM1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HUVEC cell line	Homo sapiens
Treatment: shMETTL3 HUVEC cells Control: shScramble HUVEC cells		GSE157544
Regulation		logFC: -6.28E-01 p-value: 1.94E-05
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.03E+00	GSE60213

Lung cancer [ICD-11: 2C25]

In total 3 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Chloroquine		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, ATG7, LC3B, and Sequestosome-1 (SQSTM1). beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Gefitinib		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, ATG7, LC3B, and Sequestosome-1 (SQSTM1). beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Experiment 3 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Beta-Elemen		Phase 3	Drug Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, ATG7, LC3B, and Sequestosome-1 (SQSTM1). beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.

Serine/threonine-protein kinase 4 (STK4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: 7.22E-01 p-value: 1.68E-60
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.45E+00	GSE60213

Thyroid Cancer [ICD-11: 2D10]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[107]
Responsed Disease	Thyroid Cancer [ICD-11: 2D10]
Target Regulation	Down regulation
Response Summary	Silencing METTL3 suppresses miR-222-3p expression and thus stimulates Serine/threonine-protein kinase 4 (STK4) expression, thereby repressing the malignancy and metastasis of Thyroid Carcinoma.

Serine/threonine-protein kinase mTOR (MTOR)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Liver	Mus musculus
Treatment: Mettl3 knockout liver Control: Wild type liver cells		GSE198512
Regulation		logFC: 8.34E-01 p-value: 1.58E-02
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.47E+00	GSE60213

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[108]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	5 × 10⁶ A549 cells overexpressing METTL3 (Lv-METTL3) or control (Lv-Ctrl) were suspended in 100?uL phosphate-buffered saline (PBS), and were subcutaneously injected into mouse lower right flank. Drug treatment started in the Lv-METTL3 group when the tumour volume reached around 100 mm³. Mice were randomly divided into three groups to receive vehicle, GSK2536771 (30 mg/kg) or rapamycin (1 mg/kg). Drugs were administrated daily through intraperitoneal injection for 18 days. Treatment conditions were chosen as previously reported.
Response Summary	METTL3-mediated m6 A methylation promotes lung cancer progression via activating PI3K/AKT/Serine/threonine-protein kinase mTOR (MTOR) pathway.

Renal cell carcinoma [ICD-11: 2C90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[109]
Responsed Disease	Renal cell carcinoma [ICD-11: 2C90]
Target Regulation	Down regulation
Cell Process	Epithelial-to-mesenchymal transition
Cell Process	Arrest cell cycle at G0/G1 phase
In-vitro Model	ACHN	Papillary renal cell carcinoma	Homo sapiens	CVCL_1067
	Caki-1	Clear cell renal cell carcinoma	Homo sapiens	CVCL_0234
	Caki-2	Papillary renal cell carcinoma	Homo sapiens	CVCL_0235
	HK2	Normal	Acipenser baerii	CVCL_YE28
In-vivo Model	Cells (5×10⁶ cells in 200 uL) were suspended with 100 uL PBS and 100 uL Matrigel Matrix, and injected subcutaneously into the left armpit of each mouse.
Response Summary	Knockdown of METTL3 could obviously promote cell proliferation, migration and invasion function, and induce G0/G1 arrest,METTL3 acts as a novel marker for tumorigenesis, development and survival of RCC. Knockdown of METTL3 promoted changes in pI3K/AKT/Serine/threonine-protein kinase mTOR (MTOR) markers' expression with a gain in p-PI3k, p-AKT, p-mTOR and p-p70, and a loss of p-4EBP1.

Retina cancer [ICD-11: 2D02]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[44]
Responsed Disease	Retinoblastoma [ICD-11: 2D02.2]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
	mTOR signaling pathway			hsa04150
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	WERI-Rb-1	Retinoblastoma	Homo sapiens	CVCL_1792
	Y-79	Retinoblastoma	Homo sapiens	CVCL_1893
In-vivo Model	To establish a subcutaneous tumour model in nude mice, 2 × 10⁷ Y79 cells (METTL3 knockdown group: shNC, shRNA1 and shRNA2; METTL3 up-regulated group: NC and METLL3) were resuspended in 1 mL of pre-cooled PBS, and 200 uL of the cell suspension was injected subcutaneously into the left side of the armpit to investigate tumour growth (4 × 10⁶ per mouse).
Response Summary	METTL3 promotes the progression of retinoblastoma through PI3K/AKT/Serine/threonine-protein kinase mTOR (MTOR) pathways in vitro and in vivo. METTL3 has an impact on the PI3K-AKT-mTOR-P70S6K/4EBP1 pathway. The cell proliferation results show that the stimulatory function of METTL3 is lost after rapamycin treatment.

Non-alcoholic fatty liver disease [ICD-11: DB92]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[110]
Responsed Disease	Non-alcoholic fatty liver disease [ICD-11: DB92]
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway	hsa04150
	HIF-1 signaling pathway	hsa04066
In-vivo Model	The 8-10 weeks old mice were fed either a high fat diet or HF-CDAA , ad lib for 6-12 weeks. Chow diet was used as control for HFD.The mouse liver was perfused with PBS through portal vein, and liver tissue was cut into small pieces by a scissor. The single cell was made using syringe plunger to mull the tissue, and passed through a 40 uM cell strainer.
Response Summary	The contribution of METTL3-mediated m6A modification of Ddit4 mRNA to macrophage metabolic reprogramming in non-alcoholic fatty liver disease and obesity. In METTL3-deficient macrophages, there is a significant downregulation of Serine/threonine-protein kinase mTOR (MTOR) and nuclear factor Kappa-B (NF-Kappa-B) pathway activity in response to cellular stress and cytokine stimulation, which can be restored by knockdown of DDIT4.

Signal transducer and activator of transcription 2 (STAT2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -1.27E+00 p-value: 1.09E-100
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.27E+00	GSE60213

Congenital pneumonia [ICD-11: KB24]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[111]
Responsed Disease	Congenital pneumonia [ICD-11: KB24]
Target Regulation	Down regulation
Cell Process	Cell apoptosis
In-vitro Model	WI-38	Normal	Homo sapiens	CVCL_0579
In-vivo Model	All mice were housed under a 12 h light/dark cycle with constant temperature about 25 ℃ and relative humidity approximating 55 %. The mice had free access to food and water for 10 days prior to the experiment. Forty mice were randomly selected and divided into four groups of 10 mice each. After 10 days, mice received an intraperitoneal injection of 22 mg / mL sodium pentobarbital (diluted in saline) followed by 167 uM LPS (60 uL) Saline solution was instilled into the oral cavity through the posterior pharyngeal wall. Pinch the nares quickly and hold for 30 s, model is successful when all fluid is absorbed into the nasal cavity, and slight tracheal rales appear. Lentiviral vectors containing pcDNA-SNHG4 (150 uM) or pcDNA-3.1 were intratracheally injected into mice. Twenty-one days after establishing the model, mice were intraperitoneally injected with 3% sodium pentobarbital and euthanized by overdose anesthesia at a dose of 90 mL/Kg, and organs and tissues were removed for follow-up studies.
Response Summary	SNHG4 was downregulated in the neonatal pneumonia patient serum and its overexpression could inhibit LPS induced inflammatory injury in human lung fibroblasts and mouse lung tissue. The molecular mechanism underlying this protective effect was achieved by suppression of METTL3-mediated m6A modification levels of YTHDF1-dependent Signal transducer and activator of transcription 2 (STAT2) mRNA.

Stearoyl-CoA desaturase (SCD)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: METTL3 knockdown MDA-MB-231 cells Control: MDA-MB-231 cells		GSE70061
Regulation		logFC: -1.10E+00 p-value: 2.11E-02
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.17E+00	GSE60213

Non-alcoholic fatty liver disease [ICD-11: DB92]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[112]
Responsed Disease	Non-alcoholic fatty liver disease [ICD-11: DB92]
Target Regulation	Up regulation
Pathway Response	Glycerolipid metabolism			hsa00561
Cell Process	Lipid metabolism
In-vitro Model	LM3	Malignant neoplasms	Mus musculus	CVCL_D269
In-vitro Model	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
In-vivo Model	Mice with a Tmem30a deletion specifically in pancreatic beta cells were generated as previously described. Mice developed with NAFLD were named for Tmem30a-associated NAFLD (TAN) mice. The littermate mice with genotypes of Tmem30a^loxP/loxP were used as controls.
Response Summary	Targeting METTL3/14 in vitro increases protein level of ACLY and Stearoyl-CoA desaturase (SCD) as well as triglyceride and cholesterol production and accumulation of lipid droplets. These findings demonstrate a new NAFLD mouse model that provides a study platform for DM2-related NAFLD and reveals a unique epitranscriptional regulating mechanism for lipid metabolism via m6A-modified protein expression of ACLY and SCD1.

TNF receptor-associated factor 5 (TRAF5)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -7.59E-01 p-value: 1.50E-05
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.24E+00	GSE60213

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[113]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Oxaliplatin		Approved	Drug Info
Target Regulation	Down regulation
In-vitro Model	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vivo Model	HCT-116 cells (3 × 10⁵ cells in 200 uL of saline) were subcutaneously injected into the nude mice to establish xenograft tumors. After 10 days, 10 mg/kg OX or saline was intraperitoneally injected (n = 5 for each group). Si-METTL3 or si-TRAF5 (10 nmol/20 g body weight) was injected twice intratumorally before the start of OX treatment. The mice were examined every 2 days and sacrificed 4 weeks after the OX treatment.
Response Summary	2-polarized tumor-associated macrophages enabled the oxaliplatin resistance via the elevation of METTL3-mediated m6A modification in Colorectal Cancer cells. Furthermore, they found that TNF receptor-associated factor 5 (TRAF5) contributes to the METTL3-triggered OX resistance in CRC cells.

TNF receptor-associated factor 6 (TRAF6)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 1.02E+00 p-value: 2.31E-81
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.04E+00	GSE60213

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[114]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Up regulation
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	NHOst (Normal human osteoblast cells)
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
In-vivo Model	For mouse xenograft tumor model, 1×10⁶ Saos₂ or HOS cells were mixed in 200 ul PBS and injected subcutaneously into 6- to 8-week-old C57BL/6 mice.umor size of mice was measured by vernier calipers every week after injection. The mice were euthanized after 28 days by intraperitoneal injection of 1% pentobarbital sodium (120 mg/kg), and the tumor tissues were removed from the mice.
Response Summary	METTL3 is highly expressed in OS and enhances TNF receptor-associated factor 6 (TRAF6) expression through m6A modification, thereby promoting the metastases of OS cells.

Transcription factor AP-2 gamma (TFAP2C)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Embryonic stem cells	Mus musculus
Treatment: METTL3-/- mESCs Control: Wild type ESCs		GSE147849
Regulation		logFC: 1.20E+00 p-value: 4.47E-08
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.28E+00	GSE60213

Testicular cancer [ICD-11: 2C80]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[115]
Responsed Disease	Testicular cancer [ICD-11: 2C80]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	DNA repair
In-vitro Model	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012
In-vivo Model	Male mice were subcutaneously injected with tumour cells near the limbs to establish xenografts (1 × 10⁶/mouse, 0.2 mL for each injection site; METTL3-overexpressing TCam-2/CDDP cells were inoculated once at the initial time and IGF2BP1-inhibited TCam-2/CDDP cells were inoculated every 3 days).
Response Summary	METTL3 potentiates resistance to cisplatin through m6A modification of Transcription factor AP-2 gamma (TFAP2C) in seminoma. Enhanced stability of TFAP2C mRNA promoted seminoma cell survival under cisplatin treatment burden probably through up-regulation of DNA repair-related genes. IGF2BP1 binds to TFAP2C and enhances TFAP2C mRNA stability.

Transcription factor E2F1 (E2F1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: 8.59E-01 p-value: 2.73E-57
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.01E+00	GSE60213

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[80]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Pathway Response	p53 signaling pathway	hsa04115
	Central carbon metabolism in cancer	hsa05230
	PD-L1 expression and PD-1 checkpoint pathway in cancer	hsa05235
Response Summary	This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher programmed death-ligand 1 (PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, Transcription factor E2F1 (E2F1) targets were significantly enriched.

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[116]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	MCF7-DoxR (Adriamycin-resistant cell line MCF7-DoxR)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
In-vivo Model	Once the tumor volume increased to about 1 cm3, six groups of MCF7 bearing mice (n = 10 in each group) were injected with PBS (0.1 ml, caudal vein) and adriamycin (0.1 ml, 10 mg/kg), respectively. When the tumor reached 1.5 cm in any direction (defined as event-free survival analysis), 10 mice in each group were selected to measure the tumor size and weight on the 12th day after adriamycin injection.
Response Summary	METTL3 can regulate the expression of MALAT1 through m6A, mediate the Transcription factor E2F1 (E2F1)/AGR2 axis, and promote the adriamycin resistance of breast cancer.

Transcription factor EB (TFEB)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LNCaP cell line	Homo sapiens
Treatment: shMETTL3 LNCaP cells Control: shControl LNCaP cells		GSE147884
Regulation		logFC: -6.54E-01 p-value: 8.08E-07
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 8.22E+00	GSE60213

Ischemic heart disease [ICD-11: BA40-BA6Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[117]
Responsed Disease	Ischemic heart disease [ICD-11: BA40-BA6Z]
Target Regulation	Down regulation
Pathway Response	Apoptosis			hsa04210)
Cell Process	Cell proliferation
In-vitro Model	H9c2(2-1)	Normal	Rattus norvegicus	CVCL_0286
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	To cause I/R injury, mice were subjected to 30 min of LAD ischemia followed by 60 min of reperfusion.
Response Summary	METTL3 methylates Transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy genes, at two m6A residues in the 3'-UTR, which promotes the association of the RNA-binding protein HNRNPD with TFEB pre-mRNA and subsequently decreases the expression levels of TFEB. METTL3-ALKBH5 and autophagy, providing insight into the functional importance of the reversible mRNA m6A methylation and its modulators in ischemic heart disease.

Transcription factor ISGF-3 components p91/p84 (Stat1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Raw 264.7 cell line	Mus musculus
Treatment: METTL3 knockout Raw 264.7 cells Control: Wild type Raw 264.7 cells		GSE162248
Regulation		logFC: -7.90E-01 p-value: 1.53E-25
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.34E+00	GSE60213

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[118]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 10⁶ CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Transcription factor ISGF-3 components p91/p84 (Stat1) and Irf1 mRNA via Ythdf2.

Transcription factor JunB (JUNB)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	ARPE-19 cell line	Homo sapiens
Treatment: shMETTL3 ARPE-19 cells Control: shControl ARPE-19 cells		GSE202017
Regulation		logFC: -8.92E-01 p-value: 4.99E-05
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.95E+00	GSE60213

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[119]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulation	Up regulation
Pathway Response	Cytokine-cytokine receptor interaction			hsa04060
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vitro Model	LC-2/ad	Lung adenocarcinoma	Homo sapiens	CVCL_1373
Response Summary	m6A methyltransferase METTL3 is indispensable for TGF-beta-induced EMT of lung cancer cells through the regulation of Transcription factor JunB (JUNB).

Transcription factor SOX-2 (SOX2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 5.94E-01 p-value: 9.57E-57
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 6.08E+00	GSE60213

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[120]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Target Regulation	Up regulation
Pathway Response	Signaling pathways regulating pluripotency of stem cells	hsa04550
Cell Process	DNA repair
	Nucleotide excision repair (hsa03420)
In-vitro Model	Mouse immortalized astrocytes (A type of glial cell)
Response Summary	GBM tumors have elevated levels of METTL3 transcripts and silencing METTL3 in U87/TIC inhibited tumor growth in an intracranial orthotopic mouse model with prolonged mice survival. The exogenous overexpression of 3'UTR-less Transcription factor SOX-2 (SOX2) significantly alleviated the inhibition of neurosphere formation observed in METTL3 silenced GSCs.

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[121]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	Signaling pathways regulating pluripotency of stem cells			hsa04550
Cell Process	Cell self-renewal
	Stem cell frequency
	Cell migration
In-vitro Model	CCD-112CoN	Normal	Homo sapiens	CVCL_6382
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	LS174T	Colon adenocarcinoma	Homo sapiens	CVCL_1384
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
Response Summary	METTL3, acting as an oncogene, maintained Transcription factor SOX-2 (SOX2) expression through an m6A-IGF2BP2-dependent mechanism in CRC cells, and indicated a potential biomarker panel for prognostic prediction in Colorectal carcinoma.

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[122]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
Response Summary	Knockdown of METTL3 downregulated protein levels of Transcription factor SOX-2 (SOX2), CD133 and CD44 in MCF-7 cells. METTL3 is upregulated in breast cancer, and it promotes the stemness and malignant progression of BCa through mediating m6A modification on SOX2 mRNA.

Transcriptional coactivator YAP1 (YAP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LNCaP cell line	Homo sapiens
Treatment: shMETTL3 LNCaP cells Control: shControl LNCaP cells		GSE147884
Regulation		logFC: 6.80E-01 p-value: 6.99E-58
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.22E+00	GSE60213

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[123]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Cell Process	Cell proliferation
Cell Process	Cell metastasis
In-vitro Model	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
	GES-1	Normal	Homo sapiens	CVCL_EQ22
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
Response Summary	The expression of m6A and METTL3 was upregulated in human gastric cancer tissues and gastric cancer cell lines. m6A methyltransferase METTL3 promoted the proliferation and migration of gastric cancer cells through the m6A modification of Transcriptional coactivator YAP1 (YAP1).

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[124]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell invasion
	Cell migration
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In-vivo Model	BALB/c nude mice (4 weeks old) were acquired from Vital River Laboratory (Beijing, China). HCT116 cells with stable circ1662 expression (2 × 10⁶ in 100 L of PBS) were injected via the tail vein. After 45 days, the mice were sacrificed. The lung metastatic carcinoma specimens were processed into paraffin-embedded sections for subsequent H&E staining and IHC.
Response Summary	METTL3-induced circ1662 promoted colorectal cancer cell invasion and migration by accelerating Transcriptional coactivator YAP1 (YAP1) nuclear transport. Circ1662 enhanced CRC invasion and migration depending on YAP1 and SMAD3. This result implies that circ1662 is a new prognostic and therapeutic marker for CRC metastasis.

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[125]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell migration and invasion
In-vitro Model	Homo sapiens (SK-HEP-1-Luc (luciferase labeled) cells were obtained from OBIO (Shanghai, China).)
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	1 × 10⁷ SK-HEP-1-Luc-shControl or SK-HEP-1-Luc-shMETTL3 stable cells were suspended in 300 uL of PBS and injected orthotopically into the left liver lobe of nude mice.
Response Summary	m6A methylation plays a key role in VM formation in HCC. METTL3 and Transcriptional coactivator YAP1 (YAP1) could be potential therapeutic targets via impairing VM formation in anti-metastatic strategies.

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[126]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 10⁶ lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-Transcriptional coactivator YAP1 (YAP1) axis to induce Non-small cell lung cancer drug resistance and metastasis.

Translocation protein SEC62 (SEC62)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	CT26 cell line	Mus musculus
Treatment: METTL3 knockout CT26 cells Control: CT26 cells		GSE142589
Regulation		logFC: -8.61E-01 p-value: 1.21E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.99E+00	GSE60213

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[127]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Pathway Response	Protein processing in endoplasmic reticulum			hsa04141
Cell Process	RNA stability
Cell Process	Cell apoptosis
In-vitro Model	GES-1	Normal	Homo sapiens	CVCL_EQ22
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
Response Summary	miR-4429 prevented gastric cancer progression through targeting METTL3 to inhibit m6A-caused stabilization of Translocation protein SEC62 (SEC62), indicating miR-4429 as a promising target for treatment improvement for Gastric cancer. METTL3 interacted with SEC62 to induce the m6A on SEC62 mRNA, therefore facilitated the stabilizing effect of IGF2BP1 on SEC62 mRNA.

Colorectal cancer [ICD-11: 2B91]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[128]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Fluorouracil		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Protein degradation
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
In-vivo Model	DLD-1 cells were subcutaneously implanted into 4-6 weeks old female nude mice. When tumors reached a size of about 50 mm³, the nude mice were randomly divided into 6 groups.
Response Summary	Translocation protein SEC62 (SEC62) upregulated by the METTL3-mediated m6A modification promotes the stemness and chemoresistance of colorectal cancer by binding to beta-catenin and enhancing Wnt signalling. Depletion of Sec62 sensitized the CRC cells to 5-Fu or oxaliplatin treatment.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[128]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Oxaliplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Protein degradation
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
In-vivo Model	DLD-1 cells were subcutaneously implanted into 4-6 weeks old female nude mice. When tumors reached a size of about 50 mm³, the nude mice were randomly divided into 6 groups.
Response Summary	Translocation protein SEC62 (SEC62) upregulated by the METTL3-mediated m6A modification promotes the stemness and chemoresistance of colorectal cancer by binding to beta-catenin and enhancing Wnt signalling. Depletion of Sec62 sensitized the CRC cells to 5-Fu or oxaliplatin treatment.

Tumor necrosis factor (TNF/TNF-alpha)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Raw 264.7 cell line	Mus musculus
Treatment: METTL3 knockout Raw 264.7 cells Control: Wild type Raw 264.7 cells		GSE162248
Regulation		logFC: -8.06E-01 p-value: 1.88E-29
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 4.17E+00	GSE60213

B-cell lymphomas [ICD-11: 2A86]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[10]
Responsed Disease	B-cell lymphomas [ICD-11: 2A86]
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell proliferation and metastasis
	Cell apoptosis
In-vitro Model	ATDC-5	Mouse teratocarcinoma	Mus musculus	CVCL_3894
In-vivo Model	For MIA + SAH control, S-adenosylhomocysteine (SAH), Mettl3 inhibitor (10 mg/kg) (MCE, NJ, USA) was injected intraperitoneally before MIA injection and maintained twice a week until mice were sacrificed.
Response Summary	Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) induced temporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by Tumor necrosis factor (TNF/TNF-alpha) stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Bcl2 signal axis which provides promising therapeutic strategy for temporomandibular joint osteoarthritis.

Dentofacial anomalies [ICD-11: DA0E]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[10]
Responsed Disease	Temporomandibular joint disorders [ICD-11: DA0E.8]
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell proliferation and metastasis
	Cell apoptosis
In-vitro Model	ATDC-5	Mouse teratocarcinoma	Mus musculus	CVCL_3894
In-vivo Model	For MIA + SAH control, S-adenosylhomocysteine (SAH), Mettl3 inhibitor (10 mg/kg) (MCE, NJ, USA) was injected intraperitoneally before MIA injection and maintained twice a week until mice were sacrificed.
Response Summary	Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) induced temporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by Tumor necrosis factor (TNF/TNF-alpha) stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Bcl2 signal axis which provides promising therapeutic strategy for temporomandibular joint osteoarthritis.

Tumor protein 63 (TP63)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 4.35E+00 p-value: 1.15E-34
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 6.67E+00	GSE60213

Cutaneous squamous cell carcinoma [ICD-11: 2C31]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[129]
Responsed Disease	Cutaneous squamous cell carcinoma [ICD-11: 2C31.Z]
Target Regulation	Up regulation
Pathway Response	Signaling pathways regulating pluripotency of stem cells			hsa04550
Cell Process	Cell proliferation
In-vitro Model	A-431	Skin squamous cell carcinoma	Homo sapiens	CVCL_0037
In-vitro Model	HSC-1	Skin squamous cell carcinoma	Homo sapiens	CVCL_2807
In-vivo Model	2 × 10⁶ cells were suspended in 150 uL DMEM. The A431 cells (scrambled group and shRNA1 group) were injected subcutaneously into the flanks of nude mice.
Response Summary	METTL3 knock down and methylation inhibitor cycloleucine could decrease the m6A levels and the expression of DeltaNp63 in Cutaneous squamous cell carcinoma.

Tyrosine-protein kinase JAK2 (JAK2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Raw 264.7 cell line	Mus musculus
Treatment: METTL3 knockout Raw 264.7 cells Control: Wild type Raw 264.7 cells		GSE162248
Regulation		logFC: -7.87E-01 p-value: 4.26E-20
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 7.70E+00	GSE60213

Atherosclerosis [ICD-11: BD40]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[130]
Responsed Disease	Atherosclerosis [ICD-11: BD40.Z]
Target Regulation	Up regulation
Pathway Response	JAK-STAT signaling pathway			hsa04630
Cell Process	Cell proliferation and migration
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
In-vivo Model	The adeno-associated viruses (AAV) that could silence METTL3 (sh-METTL3) and the negative control adeno-associated viruses (sh-NC) were obtained from WZ Biosciences Inc. (Jinan, China). APOE^-/- mice were randomly divided into AS + sh-NC and AS + sh-METTL3 groups. Each group contains five mice. Mice were fed with the standard diet for 1 week to acclimatize. After 1 week of acclimation, mice were challenged with a high-fat and high-cholesterol feed H10540 (Beijing HFK BIOSCIENCE Co., Ltd., Beijing, China). The formula of the H10540 feed was shown in Supplementary File S1. After 8 weeks of HFD feeding, sh-NC or sh-METTL3 adeno-associated virus serotype 9 (AAV9, 1012 viral genome copies per mouse) were respectively delivered into mice in AS + sh-NC or AS + sh-METTL3 group through tail vein injection. At 14 weeks after HDF feeding, mice fasted overnight.
Response Summary	METTL3 knockdown prevented Atherosclerosis progression by inhibiting Tyrosine-protein kinase JAK2 (JAK2)/STAT3 pathway via IGF2BP1.

Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 6.17E-01 p-value: 3.67E-05
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 4.77E+00	GSE60213

Enterovirus [ICD-11: 1A2Y]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[7]
Responsed Disease	Enterovirus [ICD-11: 1A2Y]
Target Regulation	Up regulation
Pathway Response	Autophagy	hsa04140
Cell Process	Cell proliferation and metastasis
	Cell apoptosis
	Cell autophagy
In-vitro Model	Schwann cells (A type of glial cell that surrounds neurons)
Response Summary	Knocking down METTL3 prevented Enterovirus 71-induced cell death and suppressed Enterovirus 71-induced expression of Bax while rescuing Bcl-2 expression after Enterovirus 71 infection. Knocking down METTL3 inhibited Enterovirus 71-induced expression of Atg5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) and LC3 II. Knocking down METTL3 inhibited Enterovirus 71-induced apoptosis and autophagy.

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[17]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib	Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), ATG12, and ATG16L1.

Lung cancer [ICD-11: 2C25]

In total 3 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Chloroquine		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Gefitinib		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
Experiment 3 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Beta-Elemen		Phase 3	Drug Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.

Osteoarthritis [ICD-11: FA05]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[131]
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular senescence
	Cell autophagy
In-vitro Model	C-28/I2	Normal	Homo sapiens	CVCL_0187
	FLS (Rat fibroblast synovial cell line)
In-vivo Model	Mice were anaesthetized with isoflurane supplied in a mouse anaesthesia apparatus, followed with joint surgery on the right joint by sectioning the medial meniscotibial ligament.
Response Summary	In osteoarthritis METTL3-mediated m6A modification decreased the expression of autophagy-related 7, an E-1 enzyme crucial for the formation of autophagosomes, by attenuating its RNA stability. Silencing METTL3 enhanced autophagic flux and inhibited Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) expression in OA-FLS.

Ubiquitin-like protein ATG12 (ATG12)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Mouse testis	Mus musculus
Treatment: Mettl3 knockout mouse testis Control: Mouse testis		GSE99771
Regulation		logFC: -2.94E+00 p-value: 6.14E-05
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.85E+00	GSE60213

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[17]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib	Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, ATG7, Ubiquitin-like protein ATG12 (ATG12), and ATG16L1.

Zinc finger and BTB domain-containing protein 4 (ZBTB4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 8.19E-01 p-value: 3.59E-20
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.32E+00	GSE60213

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[132]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulation	Down regulation
Pathway Response	RNA degradation	hsa03018
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	HBE (Human bronchial epithelial cell line)
In-vivo Model	Male BALB/c mice were grouped into control, CS, CS+AAV-ShMETTL3, and CS+AAV-NC shRNA groups, n = 6 animals per group. Mice in the AAV-ShMETTL3 and AAV-NC shRNA (GeneChem, China) groups were dosed by intranasal instillation after CS exposure for 4 weeks.
Response Summary	METTL3-mediated m6A modification of Zinc finger and BTB domain-containing protein 4 (ZBTB4) via EZH2 is involved in the CS-induced EMT and in lung cancer.

Zinc finger MYM-type protein 1 (ZMYM1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Liver	Mus musculus
Treatment: Mettl3 knockout liver Control: Wild type liver cells		GSE198513
Regulation		logFC: 7.91E-01 p-value: 6.45E-05
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.20E+00	GSE60213

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[133]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Pathway Response	Cytokine-cytokine receptor interaction			hsa04060
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	GES-1	Normal	Homo sapiens	CVCL_EQ22
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	MKN28	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_1416
	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
In-vivo Model	The luciferase signal intensity from days 7 to 42 is on equivalent scales in the models. Bioluminescent flux (photons/s/cm2/steradian) was determined for the lung metastases.
Response Summary	The m6A modification of Zinc finger MYM-type protein 1 (ZMYM1) mRNA by METTL3 enhanced its stability relying on the "reader" protein HuR (also known as ELAVL1) dependent pathway.The study uncover METTL3/ZMYM1/E-cadherin signaling as a potential therapeutic target in anti-metastatic strategy against Gastric cancer.

Zinc finger protein 750 (ZNF750)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Liver	Mus musculus
Treatment: Mettl3-deficient liver Control: Wild type liver cells		GSE197800
Regulation		logFC: 1.24E+00 p-value: 8.99E-10
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 5.92E+00	GSE60213

Nasopharyngeal carcinoma [ICD-11: 2B6B]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[134]
Responsed Disease	Nasopharyngeal carcinoma [ICD-11: 2B6B]
Target Regulation	Down regulation
Cell Process	Cell apoptosis
In-vitro Model	5-8F	Nasopharyngeal carcinoma	Homo sapiens	CVCL_C528
	6-10B	Nasopharyngeal carcinoma	Homo sapiens	CVCL_C529
	C666-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_7949
	HNE-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_0308
	HONE-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_8706
	NP69 (A human immortalized nasopharyngeal epithelial)
	S18	Nasopharyngeal carcinoma	Homo sapiens	CVCL_B0U9
	S26	Nasopharyngeal carcinoma	Homo sapiens	CVCL_B0UB
	SUNE1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_6946
In-vivo Model	BALB/c-nu mice (4-6 weeks old, female) were purchased from Charles River Laboratories (Beijing, China), and SUNE1-vector-luciferase or SUNE1-ZNF750-luciferase cells (1 × 10⁶) were subcutaneously injected into the dorsal or ventral flank.
Response Summary	m6A modifications maintained the low expression level of ZNF750 in NPC. Knocking down METTL3 stimulated endogenous Zinc finger protein 750 (ZNF750) expression, and vice versa.

Zinc finger protein GLI1 (GLI1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HUVEC cell line	Homo sapiens
Treatment: shMETTL3 HUVEC cells Control: shScramble HUVEC cells		GSE157544
Regulation		logFC: 7.30E-01 p-value: 2.91E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 7.23E+00	GSE60213

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[135]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Up regulation
Pathway Response	Hedgehog signaling pathway			hsa04340
Cell Process	Cell proliferation
	Cell survival
	Cell colony formation
	Cell invasion
In-vitro Model	LNCaP C4-2	Prostate carcinoma	Homo sapiens	CVCL_4782
	LNCaP C4-2B	Prostate carcinoma	Homo sapiens	CVCL_4784
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
In-vivo Model	Equal number of PC-3 cells was injected subcutaneously into right flank.
Response Summary	METTL3 silence decreased the m6A modification and expression of Zinc finger protein GLI1 (GLI1), an important component of hedgehog pathway, which led to cell apoptosis.the m6A methyltransferase METTL3 promotes the growth and motility of prostate cancer cells by regulating hedgehog pathway.

FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	ARPE-19 cell line	Homo sapiens
Treatment: shMETTL3 ARPE-19 cells Control: shControl ARPE-19 cells		GSE202017
Regulation		logFC: 1.16E+00 p-value: 1.63E-05
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 5.78E+00	GSE60213

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[136]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulation	Up regulation
Cell Process	Cell migration and proliferation
In-vitro Model	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	HaCaT	Normal	Homo sapiens	CVCL_0038
	HT-3	Cervical carcinoma	Homo sapiens	CVCL_1293
	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
In-vivo Model	A total 5 × 10⁶ stably transfected SiHa cells were subcutaneously injected into the flank of nude mice.
Response Summary	METTL3/FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) accelerates cervical cancer progression via a m6A-dependent modality, which serves as a potential therapeutic target for cervical cancer.

KRT7-AS

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HUVEC cell line	Homo sapiens
Treatment: shMETTL3 HUVEC cells Control: shScramble HUVEC cells		GSE157544
Regulation		logFC: -5.89E-01 p-value: 3.54E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 8.95E+00	GSE60213

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[137]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
Cell Process	Lung Metastasis
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
In-vitro Model	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
In-vivo Model	First, subcutaneous transplanted model was used to evaluate the growth of BT-549LMF3 and BT-549 cells. Cells (5 × 10⁶ per mouse, n = 5 for each group) were diluted in 200 ul PBS + 200 ul Matrigel (BD Biosciences) and subcutaneously injected into immunodeficient female mice. Second, subcutaneous transplanted model was used to evaluate the metastasis potential of BT-549LMF3 and BT-549 cells. Cells (5 × 10⁶ per mouse, n = 5 for each group) were diluted in 200 ul PBS + 200 ul Matrigel (BD Biosciences) and subcutaneously injected into immunodeficient female mice. Third, the in vivo lung metastasis model was established by injecting with BT-549, BT-549LMF3, FTO stable BT-549LMF3, sh-METTL3 BT-549LMF3, and sh-KRT7 BT-549LMF3 stable cells (1 × 10⁶ per mouse, n = 5 for each group)
Response Summary	Specifically, increased METTL3 methylated KRT7-AS at A877 to increase the stability of a KRT7-AS/KRT7 mRNA duplex via IGF2BP1/HuR complexes. m6A promotes breast cancer lung metastasis by increasing the stability of a KRT7-AS/KRT7 mRNA duplex and translation of KRT7.

LBX2 antisense RNA 1 (LBX2-AS1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -8.54E-01 p-value: 2.13E-07
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 6.38E+00	GSE60213

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[138]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Fluorouracil		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vitro Model	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	The increased LBX2 antisense RNA 1 (LBX2-AS1) in CRC was mediated by METTL3-dependent m6A methylation. LBX2-AS1 serves as a therapeutic target and predictor of 5-FU benefit in colorectal cancer patients.

LncRNA activating regulator of DKK1 (LNCAROD)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: 9.04E-01 p-value: 2.47E-45
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 5.11E+00	GSE60213

Head and neck squamous carcinoma [ICD-11: 2B6E]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[139]
Responsed Disease	Head and neck squamous carcinoma [ICD-11: 2B6E]
Target Regulation	Up regulation
Pathway Response	Proteasome			hsa03050
Cell Process	Proteasomal degradation
In-vitro Model	C666-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_7949
	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107
	FaDu	Hypopharyngeal squamous cell carcinoma	Homo sapiens	CVCL_1218
	HK1	Nasopharyngeal carcinoma	Acipenser baerii	CVCL_YE27
	NP69 (A human immortalized nasopharyngeal epithelial)
	Tca8113	Endocervical adenocarcinoma	Homo sapiens	CVCL_6851
Response Summary	The N6-methyladenosine (m6A) modification mediated by METTL3 and METTL14 enhanced the stability of LncRNA activating regulator of DKK1 (LNCAROD) in head and neck squamous cell carcinoma cells. LNCAROD is stabilized by m6A methylation and promotes cancer progression via forming a ternary complex with HSPA1A and YBX1 in head and neck squamous cell carcinoma.

Long intergenic non-protein coding RNA 1833 (LINC01833)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	ARPE-19 cell line	Homo sapiens
Treatment: shMETTL3 ARPE-19 cells Control: shControl ARPE-19 cells		GSE202017
Regulation		logFC: 1.55E+00 p-value: 2.63E-05
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 7.09E+00	GSE60213

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[140]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	For the tumorigenicity studies, 3 × 10⁶ HCC827 cells stably expressing sh-LINC01833 or sh-NC were injected subcutaneously into the ventral side of male BALB/c nude mice in the according groups with five mice in each group. Five mice were sampled each time. Tumor size and weight were examined at 28 days after injection.
Response Summary	m6A transferase METTL3-induced Long intergenic non-protein coding RNA 1833 (LINC01833) m6A methylation promotes NSCLC progression through modulating HNRNPA2B1 expression.

Long intergenic non-protein coding RNA 958 (LINC00958)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HUVEC cell line	Homo sapiens
Treatment: shMETTL3 HUVEC cells Control: shScramble HUVEC cells		GSE157544
Regulation		logFC: -6.47E-01 p-value: 2.79E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 5.60E+00	GSE60213

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[141]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Cell Process	RNA stability
Cell Process	Lipogenesis
In-vitro Model	FOCUS	Adult hepatocellular carcinoma	Homo sapiens	CVCL_7955
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	HEp-2	Endocervical adenocarcinoma	Homo sapiens	CVCL_1906
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	QSG-7701	Endocervical adenocarcinoma	Homo sapiens	CVCL_6944
Response Summary	Long intergenic non-protein coding RNA 958 (LINC00958) sponged miR-3619-5p to upregulate hepatoma-derived growth factor (HDGF) expression, thereby facilitating Hepatocellular carcinoma lipogenesis and progression. METTL3-mediated N6-methyladenosine modification led to LINC00958 upregulation through stabilizing its RNA transcript.

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[142]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Cell Process	RNA transcript stability
In-vitro Model	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	MCF-10A	Normal	Homo sapiens	CVCL_0598
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
In-vivo Model	MCF-7 cells transfected with sh-LINC00958 or empty vector were resuspended at 2 × 10⁷ cells/mL.
Response Summary	m6A methyltransferase-like 3 (METTL3) gave rise to the upregulation of Long intergenic non-protein coding RNA 958 (LINC00958) by promoting its RNA transcript stability in breast cancer.

Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	DKO-1 cell line	Homo sapiens
Treatment: METTL3 knockdown DKO-1 cell Control: DKO-1 cell		GSE182382
Regulation		logFC: 8.20E-01 p-value: 5.93E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.28E+00	GSE60213

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[143]
Responsed Disease	Glioma [ICD-11: 2A00.0]
Target Regulation	Up regulation
Pathway Response	TNF signaling pathway			hsa04668
Cell Process	Cell proliferation and metastasis
In-vitro Model	H4	Astrocytoma	Homo sapiens	CVCL_1239
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	U87 (A primary glioblastoma cell line)
In-vivo Model	U87 cells (5 × 10⁵) transfected with an empty vector, METTL3 shRNA, or METTL3 overexpression vector were inoculated into the right frontal node of nude mice.
Response Summary	METTL3 promoted the malignant progression of IDH-wildtype gliomas and revealed important insight into the upstream regulatory mechanism of Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and NF-Kappa-B with a primary focus on m6A modification.

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[126]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 10⁶ lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.

Thymoma [ICD-11: 2C27]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[144]
Responsed Disease	Thymic epithelial tumors [ICD-11: 2C27.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Cellular senescence			hsa04218
Cell Process	Cell viability and proliferation
In-vitro Model	T1889	Thymic undifferentiated carcinoma	Homo sapiens	CVCL_D024
Response Summary	This study highlighted METTL3 as a tumor promoter in Thymic tumors and c-MYC as a promising target to be exploited for the treatment of TET. High expression of c-MYC protein is enabled by lncRNA Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), which is methylated and delocalized by METTL3. Silencing of METTL3 combined with cisplatin or c-MYC inhibitor induces cell death in TET cells. Blocking of c-MYC by using JQ1 inhibitor cooperates with METTL3 depletion in the inhibition of proliferation and induction of cell death.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[144]
Responsed Disease	Thymic epithelial tumors [ICD-11: 2C27.Y]
Responsed Drug	JQ-1		Phase 1	Drug Info
Target Regulation	Up regulation
Pathway Response	Cellular senescence			hsa04218
Cell Process	Cell viability and proliferation
In-vitro Model	T1889	Thymic undifferentiated carcinoma	Homo sapiens	CVCL_D024
Response Summary	This study highlighted METTL3 as a tumor promoter in Thymic tumors and c-MYC as a promising target to be exploited for the treatment of TET. High expression of c-MYC protein is enabled by lncRNA Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), which is methylated and delocalized by METTL3. Silencing of METTL3 combined with cisplatin or c-MYC inhibitor induces cell death in TET cells. Blocking of c-MYC by using JQ1 inhibitor cooperates with METTL3 depletion in the inhibition of proliferation and induction of cell death.

Breast cancer [ICD-11: 2C60]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[116]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	MCF7-DoxR (Adriamycin-resistant cell line MCF7-DoxR)
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
In-vivo Model	Once the tumor volume increased to about 1 cm3, six groups of MCF7 bearing mice (n = 10 in each group) were injected with PBS (0.1 ml, caudal vein) and adriamycin (0.1 ml, 10 mg/kg), respectively. When the tumor reached 1.5 cm in any direction (defined as event-free survival analysis), 10 mice in each group were selected to measure the tumor size and weight on the 12th day after adriamycin injection.
Response Summary	METTL3 can regulate the expression of Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) through m6A, mediate the E2F1/AGR2 axis, and promote the adriamycin resistance of breast cancer.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[57]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MCF-10A	Normal	Homo sapiens	CVCL_0598
Response Summary	Silencing METTL3 down-regulate Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and HMGA2 by sponging miR-26b, and finally inhibit EMT, migration and invasion in breast cancer, providing a theoretical basis for clinical treatment of breast cancer.

Chronic kidney disease [ICD-11: GB61]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[145]
Responsed Disease	Chronic kidney disease [ICD-11: GB61]
Responsed Drug	Artenimol		Approved	Drug Info
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	HK-2 [Human kidney]	Normal	Homo sapiens	CVCL_0302
In-vitro Model	HK2	Normal	Acipenser baerii	CVCL_YE28
In-vivo Model	For the unilateral ureteral obstruction (UUO) model, male C57BL/6J mice at 8 weeks of age (20-22 g body weight) were first anaesthetized with pentobarbital sodium (50 mg/kg) via intraperitoneal injection. Then, the left ureter was ligated using 3-0 silk and a left lateral incision.
Response Summary	Renal fibrosis is a key factor in chronic kidney disease (CKD). Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)/miR-145/FAK pathway was involved in the effect of dihydroartemisinin (DHA) on TGF-beta1-induced renal fibrosis in vitro and in vivo.

Kidney failure [ICD-11: GB6Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[146]
Responsed Disease	Kidney failure [ICD-11: GB6Z]
Target Regulation	Up regulation
In-vitro Model	NIT-1	Insulin tumor	Mus musculus	CVCL_3561
Response Summary	m6A modification is co-regulated by METTL3 and FTO in cadmium-treated cells. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), LncRNA-PVT1 and m6A modification could be key nodes for cadmium-induced oxidative damage, and highlight their importance as promising preventive and therapeutic targets in cadmium toxicity.

Prostate cancer associated transcript 6 (PCAT6)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	ARPE-19 cell line	Homo sapiens
Treatment: shMETTL3 ARPE-19 cells Control: shControl ARPE-19 cells		GSE202017
Regulation		logFC: 1.32E+00 p-value: 7.57E-06
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 7.42E+00	GSE60213

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[147]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Up regulation
Cell Process	RNA stability
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
In-vitro Model	LNCaP C4-2B	Prostate carcinoma	Homo sapiens	CVCL_4784
In-vivo Model	At 1 week post-injection with PC-3 cells, mice were randomly assigned to three groups (n = 8 per group): the ASO-NC group (injection with ASO negative control targeting unknown sequence, 5 nmol in 100 uL PBS for each mouse), the ASO-L group (injection with low-dose ASO targeting PCAT6, 5 nmol in 100 uL PBS for each mouse), and the ASO-H group (injection with high-dose ASO targeting PCAT6, 10 nmol in 100 uL PBS for each mouse).
Response Summary	METTL3-mediated m6A modification contributed to Prostate cancer associated transcript 6 (PCAT6) upregulation in an IGF2BP2-dependent manner. Furthermore, PCAT6 upregulated IGF1R expression by enhancing IGF1R mRNA stability through the PCAT6/IGF2BP2/IGF1R RNA-protein three-dimensional complex. The m6 A-induced PCAT6/IGF2BP2/IGF1R axis promotes PCa bone metastasis and tumor growth, suggesting that PCAT6 serves as a promising prognostic marker and therapeutic target against bone-metastatic PCa.

Small nucleolar RNA host gene 1 (SNHG1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	ARPE-19 cell line	Homo sapiens
Treatment: shMETTL3 ARPE-19 cells Control: shControl ARPE-19 cells		GSE202017
Regulation		logFC: -1.12E+00 p-value: 7.04E-06
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.90E+00	GSE60213

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[148]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Up regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
Response Summary	METTL3/Small nucleolar RNA host gene 1 (SNHG1)/miR-140-3p/UBE2C axis plays a crucial role in cancer progression and the immune response in non-small cell lung cancer.

THAP7 antisense RNA 1 (THAP7-AS1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	DKO-1 cell line	Homo sapiens
Treatment: METTL3 knockdown DKO-1 cell Control: DKO-1 cell		GSE182382
Regulation		logFC: -1.23E+00 p-value: 1.77E-02
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 5.66E+00	GSE60213

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[149]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway	hsa04151
Cell Process	Cell growth
	Cell invasion
	Cell metastasis
Response Summary	LV-sh-THAP7 antisense RNA 1 (THAP7-AS1) treatment could suppress gastric cancer growth. THAP7-AS1, transcriptionally activated by SP1 and then modified by METTL3-mediated m6A, exerts oncogenic functions, by promoting interaction between NLS and importin alpha-1 and then improving the CUL4B protein entry into the nucleus to repress the transcription of miR-22-3p and miR-320a.

A disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HUVEC cell line	Homo sapiens
Treatment: shMETTL3 HUVEC cells Control: shScramble HUVEC cells		GSE157544
Regulation		logFC: 8.11E-01 p-value: 4.51E-05
More Results	Click to View More RNA-seq Results

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[150]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	RNA stability
In-vitro Model	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
In-vivo Model	For the formation of xenograft tumors, 5 × 10⁶ AGS cells mixed in Matrigel (BD Biosciences, Franklin Lakes, NJ, USA) were subcutaneously injected into BALB/c nude mice (5-week-old male).
Response Summary	METTL3 facilitates GC progression through the A disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9)-mediated PI3K/AKT pathway.

Acetyl-CoA carboxylase 1 (ACC1/ACACA)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: METTL3 knockdown MDA-MB-231 cells Control: MDA-MB-231 cells		GSE70061
Regulation		logFC: -6.50E-01 p-value: 2.31E-03
More Results	Click to View More RNA-seq Results

Type 2 diabetes mellitus [ICD-11: 5A11]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[48]
Responsed Disease	Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulation	Up regulation
Pathway Response	Insulin resistance			hsa04931
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3^fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3^fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3^fl/fl) were used for experiments.
Response Summary	Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. The expression of Acetyl-CoA carboxylase 1 (ACC1/ACACA), Acly, Dgat2, Ehhadh, Fasn, Foxo, Pgc1a and Sirt1, which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.

Actin, aortic smooth muscle (ACTA2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -3.22E+00 p-value: 6.14E-220
More Results	Click to View More RNA-seq Results

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[151]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Cell Process	Cell proliferation
In-vitro Model	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	GES-1	Normal	Homo sapiens	CVCL_EQ22
	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
Response Summary	METTL3 knockdown decreased Actin, aortic smooth muscle (ACTA2) muscle actin. Taken together, our finding revealed that m6A methylation writer METTL3 serve as an oncogene in tumorigenesis of Gastric cancer.

Adenylate kinase 4, mitochondrial (AK4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -5.87E-01 p-value: 2.40E-51
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[152]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Tamoxifen		Approved	Drug Info
Target Regulation	Up regulation
Cell Process	Mitochondrial apoptosis
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
In-vitro Model	MCF7-TamR	Invasive breast carcinoma	Homo sapiens	CVCL_EG55
Response Summary	Adenylate kinase 4 modulates the resistance of breast cancer cells to tamoxifen through an m6A-based epitranscriptomic mechanism. Genetic depletion of METTL3 in TamR MCF-7 cells led to a diminished Adenylate kinase 4, mitochondrial (AK4) protein level and attenuated resistance to tamoxifen.

Alpha-enolase (ENO1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -8.80E-01 p-value: 3.03E-81
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[153]
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulation	Up regulation
Pathway Response	Carbon metabolism			hsa01200
Pathway Response	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glycolysis
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	NCI-H441	Lung papillary adenocarcinoma	Homo sapiens	CVCL_1561
	NCI-H292	Lung mucoepidermoid carcinoma	Homo sapiens	CVCL_0455
	NCI-H2030	Lung adenocarcinoma	Homo sapiens	CVCL_1517
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	3LL	Malignant tumors of the mouse pulmonary system	Mus musculus	CVCL_5653
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	Calu-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0608
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A-427	Lung adenocarcinoma	Homo sapiens	CVCL_1055
	16HBE14o-	Normal	Homo sapiens	CVCL_0112
In-vivo Model	KP and Mettl3^-/- mice were bred to generate KPM^-/- mice. Afterwards, the KP and KPM^-/- mice were intranasally infected under anesthesia with adeno-associated virus type 5 (AAV5) expressing Cre to initiate lung tumorigenesis along with ALKBH5-expressing AAV5 or Empty AAV5 to generate KPE, KPA, KPEM^-/- and KPAM^-/- spontaneous LUAD mouse models. For generation of LLC-based intra-pulmonary tumor mouse models, 1 × 10⁷ LLC cells were injected into C57BL/6 mice via the tail vein.For cell-derived xenograft (CDX) mouse models, 1.0 × 10⁷ H1299 or 1.5 × 10⁷ H1975 cells were subcutaneously injected into 4-6-week-old athymic nude mice. The tumors were monitored at indicated time points and isolated for further analysis after sacrifice.
Response Summary	Alpha-enolase (ENO1) positively correlated with METTL3 and global m6A levels, and negatively correlated with ALKBH5 in human Lung adenocarcinoma(LUAD). In addition, m6A-dependent elevation of ENO1 was associated with LUAD progression.

AMPK subunit alpha-1 (AMPK/PRKAA1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: 7.94E-01 p-value: 1.12E-47
More Results	Click to View More RNA-seq Results

Atherosclerosis [ICD-11: BD40]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[154]
Responsed Disease	Atherosclerosis [ICD-11: BD40.Z]
Target Regulation	Down regulation
Pathway Response	AMPK signaling pathway			hsa04152
Cell Process	Cell apoptosis
In-vitro Model	hTERT-RPE1	Normal	Homo sapiens	CVCL_4388
In-vitro Model	iHAEC	Normal	Homo sapiens	CVCL_C0EQ
Response Summary	m6A driven machinery in virus-induced vascular endothelium damage and highlight the significance of vitamin D3 in the intervention of HCMV-induced atherosclerosis. METTL3 methylates mitochondrial calcium uniporter (MCU), the main contributor to HCMV-induced apoptosis of vascular endothelial cells, at three m6A residues in the 3'-UTR. Vitamin D3 downregulated the METTL3 by inhibiting the activation of AMPK subunit alpha-1 (AMPK/PRKAA1), thereby inhibiting the m6A modification of MCU and cell apoptosis.

Anterior gradient protein 2 homolog (AGR2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -7.71E-01 p-value: 1.08E-130
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[116]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	MCF7-DoxR (Adriamycin-resistant cell line MCF7-DoxR)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
In-vivo Model	Once the tumor volume increased to about 1 cm3, six groups of MCF7 bearing mice (n = 10 in each group) were injected with PBS (0.1 ml, caudal vein) and adriamycin (0.1 ml, 10 mg/kg), respectively. When the tumor reached 1.5 cm in any direction (defined as event-free survival analysis), 10 mice in each group were selected to measure the tumor size and weight on the 12th day after adriamycin injection.
Response Summary	METTL3 can regulate the expression of MALAT1 through m6A, mediate the E2F1/Anterior gradient protein 2 homolog (AGR2) axis, and promote the adriamycin resistance of breast cancer.

ATP-citrate synthase (ACLY)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Liver	Mus musculus
Treatment: Mettl3 knockout liver Control: Wild type liver cells		GSE198513
Regulation		logFC: -6.16E-01 p-value: 1.78E-18
More Results	Click to View More RNA-seq Results

Type 2 diabetes mellitus [ICD-11: 5A11]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[48]
Responsed Disease	Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulation	Up regulation
Pathway Response	Insulin resistance			hsa04931
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3^fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3^fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3^fl/fl) were used for experiments.
Response Summary	Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. The expression of Acc1, ATP-citrate synthase (ACLY), Dgat2, Ehhadh, Fasn, Foxo, Pgc1a and Sirt1, which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.

Non-alcoholic fatty liver disease [ICD-11: DB92]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[112]
Responsed Disease	Non-alcoholic fatty liver disease [ICD-11: DB92]
Target Regulation	Up regulation
Pathway Response	Glycerolipid metabolism			hsa00561
Cell Process	Lipid metabolism
In-vitro Model	LM3	Malignant neoplasms	Mus musculus	CVCL_D269
In-vitro Model	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
In-vivo Model	Mice with a Tmem30a deletion specifically in pancreatic beta cells were generated as previously described. Mice developed with NAFLD were named for Tmem30a-associated NAFLD (TAN) mice. The littermate mice with genotypes of Tmem30a^loxP/loxP were used as controls.
Response Summary	Targeting METTL3/14 in vitro increases protein level of ATP-citrate synthase (ACLY) and SCD1 as well as triglyceride and cholesterol production and accumulation of lipid droplets. These findings demonstrate a new NAFLD mouse model that provides a study platform for DM2-related NAFLD and reveals a unique epitranscriptional regulating mechanism for lipid metabolism via m6A-modified protein expression of ACLY and SCD1.

ATP-dependent translocase ABCB1 (ABCB1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -1.24E+00 p-value: 2.14E-202
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[22]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulation	Up regulation
Cell Process	Cell growth and death
	Cell apoptosis
In-vitro Model	ADR-resistant MCF-7 (MCF-7/ADR) cells (Human breast cancer doxorubicin-resistant cell line)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
In-vivo Model	Cell suspensions (2 × 10⁶ cells/mL) made with MCF-7/ADR cells stably expressing METTL3 and/or miR-221-3p inhibitor were subcutaneously implanted into each mouse. One week later, xenografted mice were injected with 0.1 mL ADR (25 mg/kg, intraperitoneal injection) twice a week.
Response Summary	METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating pri-microRNA-221-3p maturation in a m6A-dependent manner. METTL3 knockdown was shown to reduce the expression of miR-221-3p by reducing pri-miR-221-3p m6A mRNA methylation, reducing the expression of ATP-dependent translocase ABCB1 (ABCB1) and BCRP, and inducing apoptosis. Identified the METTL3/miR-221-3p/HIPK2/Che-1 axis as a novel signaling event that will be responsible for resistance of BC cells to ADR.

Beclin-1 associated RUN domain containing protein (RUBCN/Rubicon)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: 6.54E-01 p-value: 1.80E-06
More Results	Click to View More RNA-seq Results

Non-alcoholic fatty liver disease [ICD-11: DB92]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[155]
Responsed Disease	Non-alcoholic fatty liver disease [ICD-11: DB92]
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cell autophagy
In-vitro Model	AML12	Normal	Mus musculus	CVCL_0140
	Hepa 1-6	Hepatocellular carcinoma of the mouse	Mus musculus	CVCL_0327
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	All mice were housed in specific pathogen-free conditions in the animal facility with constant temperature and humidity under a 12-h light/12-h dark cycle, with free access to water and food. After a week of adaptation, they were then divided into two groups randomly and fed with a HFD (60 kcal% fat, D12492, Research Diets) or standard normal chow diet (CD) for 16 weeks, respectively.
Response Summary	The upregulation of METTL3 and YTHDF1 induced by lipotoxicity contributes to the elevated expression level of Beclin-1 associated RUN domain containing protein (RUBCN/Rubicon) in an m6A-dependent manner, which inhibits the fusion of autophagosomes and lysosomes and further suppresses the clearance of LDs via lysosomes in nonalcoholic fatty liver disease.

Brain and muscle ARNT-like 1 (Bmal1/ARNTL)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -1.11E+00 p-value: 1.53E-46
More Results	Click to View More RNA-seq Results

Metabolic disorders [ICD-11: 5D2Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[92]
Responsed Disease	Metabolic disorders [ICD-11: 5D2Z]
Target Regulation	Up regulation
Pathway Response	Adipocytokine signaling pathway			hsa04920
Cell Process	Llipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vitro Model	Hepa 1-6	Hepatocellular carcinoma of the mouse	Mus musculus	CVCL_0327
In-vivo Model	Liver-specific Bmal1^f/f-AlbCre-knockout mice were purchased from Jackson Laboratory. C57BI/6J or Bmal1^f/f-AlbCre-knockout male mice were maintained under a 12 hr light/12 hr dark (LD) cycle (ZT0 = 6 AM) and fed ad libitum with normal rodent chow (2018 Global 18% Protein diet, Envigo) and water. At 10-14 weeks of age, 10 male mice per group were sacrificed via CO2 asphyxiation at Zeitgeber Time (ZT) 0,2,6,10,12,14,18,22. In order to induce high levels of ROS in the liver, WT male mice were fasted 12 h and followed by intraperitoneal injection with 300 mg/kg APAP dissolved in PBS and re-fed.
Response Summary	PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Hepatic deletion of Brain and muscle ARNT-like 1 (Bmal1/ARNTL) increases m6A mRNA methylation, particularly of PPaRalpha. Inhibition of m6A methylation via knockdown of m6A methyltransferase METTL3 decreases PPaR-Alpha m6A abundance and increases PPaRalpha mRNA lifetime and expression, reducing lipid accumulation in cells in vitro. YTHDF2 binds to PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Transcriptional regulation of circadian rhythms is essential for lipid metabolic homeostasis, disruptions of which can lead to metabolic diseases.

Non-alcoholic fatty liver disease [ICD-11: DB92]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[156]
Responsed Disease	Non-alcoholic fatty liver disease [ICD-11: DB92]
Target Regulation	Up regulation
In-vivo Model	M3LKO (Mettl3^fl/fl; Alb-Cre) mice were generated by crossing Mettl3^fl/fl mice (provided by Dr. Jacob Hanna) with albumin-Cre mice (Jackson Laboratories, Bar Harbor, ME), and genotypes were confirmed by tail-DNA PCR using primers as previously described.
Response Summary	Liver-specific Mettl3 knockout mice exhibited global decrease in m6A on polyadenylated RNAs and pathologic features associated with nonalcoholic fatty liver disease. Studies in the M3LKO model indicated that METTL3 exhibits pleotropic function to maintain liver homeostasis by deregulating m6A profile and expression of the liver transcriptome. A significant decrease in total Brain and muscle ARNT-like 1 (Bmal1/ARNTL) and Clock mRNAs but an increase in their nuclear levels were observed in M3LKO livers, suggesting impaired nuclear export.

C-X-C motif chemokine 10 (CXCL10)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	CT26 cell line	Mus musculus
Treatment: METTL3 knockout CT26 cells Control: CT26 cells		GSE142589
Regulation		logFC: 1.38E+00 p-value: 1.00E-07
More Results	Click to View More RNA-seq Results

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[118]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 10⁶ CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and C-X-C motif chemokine 10 (Cxcl10) in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2.

C-X-C motif chemokine 9 (CXCL9)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -2.40E+00 p-value: 4.57E-02
More Results	Click to View More RNA-seq Results

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[118]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 10⁶ CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, C-X-C motif chemokine 9 (Cxcl9), and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2.

Caspase-3 (CASP3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -7.30E-01 p-value: 2.00E-53
More Results	Click to View More RNA-seq Results

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation
Pathway Response	Apoptosis			hsa04210
	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
Response Summary	Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 (CASP3) in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and Cyclin D1.

CD44 antigen (CD44)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 1.08E+00 p-value: 6.88E-51
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[122]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
Response Summary	Knockdown of METTL3 downregulated protein levels of SOX2, CD133 and CD44 antigen (CD44) in MCF-7 cells. METTL3 is upregulated in breast cancer, and it promotes the stemness and malignant progression of BCa through mediating m6A modification on SOX2 mRNA.

Circadian locomoter output cycles protein kaput (CLOCK)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: 6.28E-01 p-value: 1.95E-19
More Results	Click to View More RNA-seq Results

Non-alcoholic fatty liver disease [ICD-11: DB92]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[156]
Responsed Disease	Non-alcoholic fatty liver disease [ICD-11: DB92]
Target Regulation	Up regulation
In-vivo Model	M3LKO (Mettl3^fl/fl; Alb-Cre) mice were generated by crossing Mettl3^fl/fl mice (provided by Dr. Jacob Hanna) with albumin-Cre mice (Jackson Laboratories, Bar Harbor, ME), and genotypes were confirmed by tail-DNA PCR using primers as previously described.
Response Summary	Liver-specific Mettl3 knockout mice exhibited global decrease in m6A on polyadenylated RNAs and pathologic features associated with nonalcoholic fatty liver disease. Studies in the M3LKO model indicated that METTL3 exhibits pleotropic function to maintain liver homeostasis by deregulating m6A profile and expression of the liver transcriptome. A significant decrease in total Bmal1 and Circadian locomoter output cycles protein kaput (CLOCK) mRNAs but an increase in their nuclear levels were observed in M3LKO livers, suggesting impaired nuclear export.

Cyclin-dependent kinase 1 (CDK1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Liver	Mus musculus
Treatment: Mettl3-deficient liver Control: Wild type liver cells		GSE197800
Regulation		logFC: 2.36E+00 p-value: 3.11E-05
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[157]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell cycle
In-vitro Model	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	HCC1806	Breast squamous cell carcinoma	Homo sapiens	CVCL_1258
	MCF-10A	Normal	Homo sapiens	CVCL_0598
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
In-vivo Model	Twelve female BALB/c nude mice (aged 4 weeks, 18-22g) were randomly divided into 2 groups. Stable circMETTL3-expression SUM1315 cells or control cells (1×10⁶ cells in 0.1 mL PBS) was subcutaneously injected into mammary fat pads of the mice and the growth of tumors was followed up every week. Tumor volume was measured every week using a caliper, calculated as (length × width²)/2. After 4 weeks, mice were sacrificed and checked for final tumor weight.
Response Summary	circMETTL3 promotes breast cancer progression through circMETTL3/miR-31-5p/Cyclin-dependent kinase 1 (CDK1) axis.

Cystine/glutamate transporter (SLC7A11)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shMETTL3 MOLM13 cells Control: MOLM13 cells		GSE98623
Regulation		logFC: -4.02E+00 p-value: 2.26E-108
More Results	Click to View More RNA-seq Results

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[158]
Responsed Disease	Hepatoblastoma [ICD-11: 2C12.01]
Target Regulation	Up regulation
Pathway Response	Ferroptosis			hsa04216
Cell Process	Ferroptosis
In-vitro Model	HuH-6	Hepatoblastoma	Homo sapiens	CVCL_4381
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	METTL3-mediated Cystine/glutamate transporter (SLC7A11) m6A modification enhances hepatoblastoma ferroptosis resistance. The METTL3/IGF2BP1/m6A modification promotes SLC7A11 mRNA stability and upregulates its expression by inhibiting the deadenylation process.

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[159]
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulation	Up regulation
Pathway Response	Ferroptosis			hsa04216
Cell Process	Ferroptosis
In-vitro Model	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H322	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1556
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	For the subcutaneous xenograft model, PC9 cells stably transfected with METTL3 knockdown (shMETTL3) or negative control (shNC) shRNA (5 × 10⁶ cells per mouse, n = 6) were suspended in 200 uL PBS with 50% Matrigel matrix (Corning, USA, 354234) and then injected into one side of the axilla of nude mice.
Response Summary	METTL3-mediated m-6A modification could stabilize Cystine/glutamate transporter (SLC7A11) mRNA and promote its translation, thus promoting LUAD cell proliferation and inhibiting cell ferroptosis, a novel form of programmed cell death.

Diacylglycerol O-acyltransferase 2 (DGAT2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shMETTL3 MOLM13 cells Control: MOLM13 cells		GSE98623
Regulation		logFC: -1.53E+00 p-value: 7.36E-18
More Results	Click to View More RNA-seq Results

Type 2 diabetes mellitus [ICD-11: 5A11]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[48]
Responsed Disease	Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulation	Up regulation
Pathway Response	Insulin resistance			hsa04931
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3^fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3^fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3^fl/fl) were used for experiments.
Response Summary	Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. The expression of Acc1, Acly, Diacylglycerol O-acyltransferase 2 (DGAT2), Ehhadh, Fasn, Foxo, Pgc1a and Sirt1, which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.

DNA damage-inducible transcript 4 protein (DDIT4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 1.24E+00 p-value: 1.11E-27
More Results	Click to View More RNA-seq Results

Obesity [ICD-11: 5B81]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[110]
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway	hsa04150
	HIF-1 signaling pathway	hsa04066
In-vivo Model	The 8-10 weeks old mice were fed either a high fat diet or HF-CDAA , ad lib for 6-12 weeks. Chow diet was used as control for HFD.The mouse liver was perfused with PBS through portal vein, and liver tissue was cut into small pieces by a scissor. The single cell was made using syringe plunger to mull the tissue, and passed through a 40 uM cell strainer.
Response Summary	The contribution of METTL3-mediated m6A modification of DNA damage-inducible transcript 4 protein (DDIT4) mRNA to macrophage metabolic reprogramming in non-alcoholic fatty liver disease and obesity. In METTL3-deficient macrophages, there is a significant downregulation of mammalian target of rapamycin (mTOR) and nuclear factor Kappa-B (NF-Kappa-B) pathway activity in response to cellular stress and cytokine stimulation, which can be restored by knockdown of DDIT4.

Non-alcoholic fatty liver disease [ICD-11: DB92]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[110]
Responsed Disease	Non-alcoholic fatty liver disease [ICD-11: DB92]
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway	hsa04150
	HIF-1 signaling pathway	hsa04066
In-vivo Model	The 8-10 weeks old mice were fed either a high fat diet or HF-CDAA , ad lib for 6-12 weeks. Chow diet was used as control for HFD.The mouse liver was perfused with PBS through portal vein, and liver tissue was cut into small pieces by a scissor. The single cell was made using syringe plunger to mull the tissue, and passed through a 40 uM cell strainer.
Response Summary	The contribution of METTL3-mediated m6A modification of DNA damage-inducible transcript 4 protein (DDIT4) mRNA to macrophage metabolic reprogramming in non-alcoholic fatty liver disease and obesity. In METTL3-deficient macrophages, there is a significant downregulation of mammalian target of rapamycin (mTOR) and nuclear factor Kappa-B (NF-Kappa-B) pathway activity in response to cellular stress and cytokine stimulation, which can be restored by knockdown of DDIT4.

Corneal injury [ICD-11: NA06]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[87]
Responsed Disease	Corneal injury [ICD-11: NA06.4]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
In-vitro Model	CGC (Conjunctival goblet cells)
In-vivo Model	Mettl3^fl/wt mice were generated as previously described. Mettl3^fl/wt mice were crossed with K14CreER mice to obtain K14^creER/Mettl3^fl/fl (cKO) mice. Mettl3 cKO and control mice were injected with tamoxifen and then were subjected to corneal alkali burn treatment. The right eye was the experimental eye, and the left eye was the control eye. The mice were sacrificed at 24 hours, 7 days, 14 days, 35 days, and 56 days after injury. Six mice were taken from each period. Both eyes were removed, frozen in OCT (n = 4), fixed in 4% paraformaldehyde, and embedded in conventional paraffin (n = 2).
Response Summary	METTL3 knockout in the limbal stem cells promotes the in vivo cell proliferation and migration, leading to the fast repair of corneal injury. In addition, m6A modification profiling identified stem cell regulatory factors AHNAK and DNA damage-inducible transcript 4 protein (DDIT4) as m6A targets.

DNA repair protein RAD51 homolog 1 (RAD51)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HeLa cell line	Homo sapiens
Treatment: METTL3 knockdown HeLa cells Control: HeLa cells		GSE70061
Regulation		logFC: 2.32E+00 p-value: 1.62E-02
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[98]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Homologous recombination			hsa03440
Cell Process	Homologous recombination repair
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
In-vivo Model	Cells were trypsinized and resuspended in DMEM at a consistence of 1 × 10⁷ cells/ml. A total of 1 × 106 cells were injected into flank of mice. 27 days after injection, tumors were removed for paraffin-embedded sections.
Response Summary	Knockdown of METTL3 sensitized these breast cancer cells to Adriamycin (ADR; also named as doxorubicin) treatment and increased accumulation of DNA damage. Mechanically, we demonstrated that inhibition of METTL3 impaired HR efficiency and increased ADR-induced DNA damage by regulating m6A modification of EGF/RAD51 axis. METTL3 promoted EGF expression through m6A modification, which further upregulated DNA repair protein RAD51 homolog 1 (RAD51) expression, resulting in enhanced HR activity.

DNA replication licensing factor MCM5 (MCM5)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -6.56E-01 p-value: 6.81E-68
More Results	Click to View More RNA-seq Results

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[42]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	GES-1	Normal	Homo sapiens	CVCL_EQ22
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
	MKN74	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_2791
	pGCC (Primary GC cells)
	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
In-vivo Model	A total of 2 × 10⁶ GC cells were injected into the flank of nude mice in a 1:1 suspension of BD Matrigel (BD Biosciences) in phosphate-buffered saline (PBS) solution.
Response Summary	In gastric cancer, several component molecules (e.g., DNA replication licensing factor MCM5 (MCM5), MCM6, etc.) of MYC target genes were mediated by METTL3 via altered m6A modification.

DNA-3-methyladenine glycosylase (ANPG/MPG)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -6.00E-01 p-value: 3.04E-08
More Results	Click to View More RNA-seq Results

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[69]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Responsed Drug	Temozolomide		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	DNA repair
In-vitro Model	U251 (Fibroblasts or fibroblast like cells)
	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
In-vivo Model	Subcutaneously injected shMETTL3 or shNC-expressing U87-MG-TMZ cells into BALB/c NOD mice. After confirmation of GBM implantation, mice were treated with TMZ (66 mg/kg/d, 5 d per week, for 3 cycles).
Response Summary	Two critical DNA repair genes (MGMT and DNA-3-methyladenine glycosylase (ANPG/MPG)) were m6A-modified by METTL3, whereas inhibited by METTL3 silencing or DAA-mediated total methylation inhibition, which is crucial for METTL3-improved temozolomide resistance in glioblastoma cells.

Dual specificity protein phosphatase 2 (DUSP2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: 7.70E-01 p-value: 1.05E-14
More Results	Click to View More RNA-seq Results

Emphysema [ICD-11: CA21]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[160]
Responsed Disease	Emphysema [ICD-11: CA21]
Target Regulation	Down regulation
Pathway Response	MAPK signaling pathway	hsa04010
Response Summary	METTL3-mediated formation of EV miR-93, facilitated by m6A, is implicated in the aberrant cross-talk of epithelium-macrophages, indicating that this process is involved in the smoking-related emphysema. EV miR-93 was used as a novel risk biomarker for CS-induced emphysema. MiR-93 activated the JNK pathway by targeting Dual specificity protein phosphatase 2 (DUSP2), which elevated the levels of matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 12 (MMP12) and induced elastin degradation, leading to emphysema.

Dual specificity protein phosphatase 5 (DUSP5)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LNCaP cell line	Homo sapiens
Treatment: shMETTL3 LNCaP cells Control: shControl LNCaP cells		GSE147884
Regulation		logFC: -7.11E-01 p-value: 1.15E-05
More Results	Click to View More RNA-seq Results

Gallbladder cancer [ICD-11: 2C13]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[161]
Responsed Disease	Gallbladder cancer [ICD-11: 2C13]
Target Regulation	Down regulation
Cell Process	Cell proliferation
	Cell invasion
	Cell migration
In-vitro Model	NOZ	Gallbladder carcinoma	Homo sapiens	CVCL_3079
	GBC-SD	Human gallbladder	Homo sapiens	CVCL_6903
Response Summary	METTL3-mediated m6A-modification profile in gallbladder-cancer cells and identified Dual specificity protein phosphatase 5 (DUSP5) as the downstream gene of METTL3. METTL3 promoted the degradation of DUSP5 mRNA in a YTHDF2-dependent manner.

E3 ubiquitin-protein ligase Mdm2 (Mdm2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 2.07E+00 p-value: 7.73E-92
More Results	Click to View More RNA-seq Results

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[28]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell apoptosis
Cell Process	Cells in G2/M phase decreased
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	NB4	Acute promyelocytic leukemia	Homo sapiens	CVCL_0005
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	MOLT-4	Adult T acute lymphoblastic leukemia	Homo sapiens	CVCL_0013
	Kasumi-1	Myeloid leukemia with maturation	Homo sapiens	CVCL_0589
	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	HL-60	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	HEL	Erythroleukemia	Homo sapiens	CVCL_0001
	CCRF-CEM C7	T acute lymphoblastic leukemia	Homo sapiens	CVCL_6825
	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	METTL3 and METTL14 play an oncogenic role in acute myeloid leukemia(AML) by targeting E3 ubiquitin-protein ligase Mdm2 (Mdm2)/p53 signal pathway. The knockdown of METTL3 and METTL14 in K562 cell line leads to several changes in the expression of p53 signal pathway, including the upregulation of p53, cyclin dependent kinase inhibitor 1A (CDKN1A/p21), and downregulation of mdm2.

E3 ubiquitin-protein ligase SMURF1 (SMURF1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HeLa cell line	Homo sapiens
Treatment: METTL3 knockdown HeLa cells Control: HeLa cells		GSE70061
Regulation		logFC: -1.08E+00 p-value: 3.04E-03
More Results	Click to View More RNA-seq Results

Inflammatory response [ICD-11: MG46]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[162]
Responsed Disease	Inflammatory response [ICD-11: MG46]
Target Regulation	Down regulation
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	RNA stability
In-vitro Model	MC3T3-E1	Normal	Mus musculus	CVCL_0409
Response Summary	METTL3 knockdown inhibits osteoblast differentiation and Smad-dependent signaling by stabilizing Smad7 and E3 ubiquitin-protein ligase SMURF1 (SMURF1) mRNA transcripts via YTHDF2 involvement and activates the inflammatory response by regulating MAPK signaling in LPS-induced inflammation.

ELAV-like protein 1 (HuR/ELAVL1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Embryonic stem cells	Mus musculus
Treatment: METTL3 knockout ESCs Control: Wild type ESCs		GSE146466
Regulation		logFC: 6.09E-01 p-value: 1.50E-08
More Results	Click to View More RNA-seq Results

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[163]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Down regulation
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
In-vivo Model	A total of 1 × 10⁶ PC3 cells or DU145 cells suspended in a mixture of 100 uL PBS and Matrigel were subcutaneously injected into BALB/c nude mice. Tumor weight were measured 2 months after the engraftment. To evaluate the role of METTL3 in tumor metastasis, PC3 cells with or without knockdown of METTL3 were injected into SCID mice through the tail vein (1 × 10⁶ cells per mouse). After eight weeks, mice were sacrificed and their lung tissues were collected for subsequent analyses.
Response Summary	m6A modification levels were markedly upregulated in human PCa tissues due to increased expression of METTL3. METTL3 mediates m6A modification of USP4 mRNA at A2696, and m6A reader protein YTHDF2 binds to and induces degradation of USP4 mRNA by recruiting RNA-binding protein HNRNPD to the mRNA. Decrease of USP4 fails to remove the ubiquitin group from ELAVL1 protein, resulting in a reduction of ELAVL1 protein. Lastly, downregulation of ELAV-like protein 1 (HuR/ELAVL1) in turn increases ARHGDIA expression, promoting migration and invasion of PCa cells.

Ephrin type-B receptor 2 (ERK/EPHB2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -6.74E-01 p-value: 5.11E-30
More Results	Click to View More RNA-seq Results

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[72]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	KM12	Colon carcinoma	Homo sapiens	CVCL_1331
Response Summary	METTL3 played a tumor-suppressive role in Colorectal cancer cell proliferation, migration and invasion through p38/Ephrin type-B receptor 2 (ERK/EPHB2) pathways, which indicated that METTL3 was a novel marker for CRC carcinogenesis, progression and survival.

Muscular dystrophies [ICD-11: 8C70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[67]
Responsed Disease	Muscular dystrophies [ICD-11: 8C70]
Target Regulation	Up regulation
Pathway Response	MAPK signaling pathway			hsa04010
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vitro Model	C2C12	Normal	Mus musculus	CVCL_0188
In-vivo Model	For mouse muscle injury and regeneration experiment, tibialis anterior (TA) muscles of 6-week-old male mice were injected with 25 uL of 10 uM cardiotoxin (CTX, Merck Millipore, 217503), 0.9% normal saline (Saline) were used as control. The regenerated muscles were collected at day 1, 3, 5, and 10 post-injection. TA muscles were isolated for Hematoxylin and eosin staining or frozen in liquid nitrogen for RNA and protein extraction.
Response Summary	m6A writers METTL3/METTL14 and the m6A reader YTHDF1 orchestrate MNK2 expression posttranscriptionally and thus control Ephrin type-B receptor 2 (ERK/EPHB2) signaling, which is required for the maintenance of muscle myogenesis and contributes to regeneration.

Epidermal growth factor receptor (EGFR)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	ARPE-19 cell line	Homo sapiens
Treatment: shMETTL3 ARPE-19 cells Control: shControl ARPE-19 cells		GSE202017
Regulation		logFC: -6.74E-01 p-value: 1.53E-03
More Results	Click to View More RNA-seq Results

Melanoma [ICD-11: 2C30]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[164]
Responsed Disease	Melanoma [ICD-11: 2C30]
Responsed Drug	PLX4032		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	EGFR tyrosine kinase inhibitor resistance			hsa01521
Cell Process	Cell apoptosis
In-vitro Model	A375-R	Amelanotic melanoma	Homo sapiens	CVCL_6234
Response Summary	METTL3 increased the m6A modification of Epidermal growth factor receptor (EGFR) mRNA in A375R cells, which promoted its translation efficiency. Inhibiting METTL3 function to restore PLX4032 sensitivity in patients with melanoma.

F-box/WD repeat-containing protein 7 (FBXW7)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: METTL3 knockdown MDA-MB-231 cells Control: MDA-MB-231 cells		GSE70061
Regulation		logFC: 7.60E-01 p-value: 3.50E-02
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[165]
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulation	Down regulation
Cell Process	RNA stability
	Cell apoptosis
In-vitro Model	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	The mice were randomly divided into groups before subcutaneous injection with cells (10⁷) suspended in 200 uL of phosphate-buffered saline. Tumors were measured on day 7 and then once every 7 days until 28 days after injection.
Response Summary	METTL3 positively regulates F-box/WD repeat-containing protein 7 (FBXW7) expression and confirm the tumor-suppressive role of m6A-modified FBXW7, thus providing insight into its epigenetic regulatory mechanisms in lung adenocarcinoma initiation and development.

Forkhead box protein C2 (FOXC2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Mesenchymal stem cell line	Mus musculus
Treatment: Mettl3 knockout mesenchymal stem cells Control: Wild type mesenchymal stem cells		GSE114933
Regulation		logFC: -2.30E+00 p-value: 6.85E-05
More Results	Click to View More RNA-seq Results

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[166]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
Response Summary	METTL3-mediated circNRIP1 exhibits oncogenic roles in osteosarcoma by regulating Forkhead box protein C2 (FOXC2) via sponging miR-199a, which provides new ideas for the treatment of osteosarcoma.

Forkhead box protein O1 (FOXO1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 9.70E-01 p-value: 7.07E-55
More Results	Click to View More RNA-seq Results

Type 2 diabetes mellitus [ICD-11: 5A11]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[48]
Responsed Disease	Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulation	Up regulation
Pathway Response	Insulin resistance			hsa04931
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3^fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3^fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3^fl/fl) were used for experiments.
Response Summary	Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. The expression of Acc1, Acly, Dgat2, Ehhadh, Fasn, Forkhead box protein O1 (FOXO1), Pgc1a and Sirt1, which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.

Forkhead box protein O3 (FOXO3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 8.00E-01 p-value: 1.28E-68
More Results	Click to View More RNA-seq Results

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[167]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	FoxO signaling pathway			hsa04068
Cell Process	Cell Transport
	Cell catabolism
	Cell autophagy
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	Hepa 1-6	Hepatocellular carcinoma of the mouse	Mus musculus	CVCL_0327
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	WRL 68	Endocervical adenocarcinoma	Homo sapiens	CVCL_0581
In-vivo Model	For the drug-resistant subcutaneous tumor models, drug administration was adopted when the tumors reached about 50 mm³ in size, at which point mice were randomized for treatment with DMSO(intraperitoneally) or sorafenib (50 mg/kg/every 2 days, intraperitoneally). For the patient-derived tumor xenograft model, drug administration began 4 weeks after tumors reached about 100 mm³ in size with sorafenib (50 mg/kg/every 3 days, intraperitoneally) or siCtrl/siMETTL3 intratumor injection.
Response Summary	METTL3 and Forkhead box protein O3 (FOXO3) levels are tightly correlated in hepatocellular carcinoma patients. In mouse xenograft models, METTL3 depletion significantly enhances sorafenib resistance of HCC by abolishing the identified METTL3-mediated FOXO3 mRNA stabilization, and overexpression of FOXO3 restores m6 A-dependent sorafenib sensitivity.

G1/S-specific cyclin-D1 (CCND1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LNCaP cell line	Homo sapiens
Treatment: shMETTL3 LNCaP cells Control: shControl LNCaP cells		GSE147884
Regulation		logFC: -6.51E-01 p-value: 1.46E-104
More Results	Click to View More RNA-seq Results

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
Response Summary	Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of AKT and expression of down-stream effectors p70S6K and G1/S-specific cyclin-D1 (CCND1).

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[168]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell cycle
	Cell apoptosis
In-vitro Model	OVCAR-3	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
Response Summary	METTL3 knockdown downregulated the phosphorylation levels of AKT and the expression of the downstream effector G1/S-specific cyclin-D1 (CCND1) in ovarian cancer.

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[169]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulation	Down regulation
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
In-vivo Model	Mice were divided into two groups (n = 4/group) randomly. 3×10⁶ cells suspended in 200 uL PBS were administered via subcutaneous injection over the right flank region of nude mice. After the development of palpable tumors (average volume, 50 mm³), intratumoral injection of synthetic miR-193b, or negative control complexed with siPORT Amine transfection reagent (Ambion, USA) was given 6 times at a 4-day interval.
Response Summary	METTL3 modulates miR-193b mature process in an m6A-dependent manner. Reintroduction of miR-193b profoundly inhibits tumorigenesis of cervical cancer cells both in vivo and in vitro through G1/S-specific cyclin-D1 (CCND1) targeting.

Obesity [ICD-11: 5B81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[170]
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulation	Up regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Mitotic clonal
	Prolonged G1/S transition
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Response Summary	Obesity is becoming a global problem. ZFP217 knockdown-induced adipogenesis inhibition was caused by G1/S-specific cyclin-D1 (CCND1), which was mediated by METTL3 and YTHDF2 in an m6A-dependent manner.

Glucose transporter type 1 (SLC2A1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: 8.54E-01 p-value: 1.08E-85
More Results	Click to View More RNA-seq Results

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[54]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	Glycolysis / Gluconeogenesis	hsa00010
Cell Process	Glucose metabolism
Response Summary	METTL3 stabilizes HK2 and Glucose transporter type 1 (SLC2A1) (GLUT1) expression in colorectal cancer through an m6A-IGF2BP2/3- dependent mechanism.

Heat shock 70 kDa protein 1A (HSPA1A)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	ARPE-19 cell line	Homo sapiens
Treatment: shMETTL3 ARPE-19 cells Control: shControl ARPE-19 cells		GSE202017
Regulation		logFC: -1.11E+00 p-value: 1.96E-02
More Results	Click to View More RNA-seq Results

Pre-eclampsia [ICD-11: JA24]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[172]
Responsed Disease	Pre-eclampsia [ICD-11: JA24]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway	hsa04310
	mTOR signaling pathway	hsa04150
Response Summary	Findings show that METTL3 and METTL14 were up-regulated in preeclampsia(PE). Heat shock 70 kDa protein 1A (HSPA1A) is involved in the pathophysiology of PE as its mRNA and protein expression is regulated by m6A modification.

Hepatocyte growth factor receptor (c-Met/MET)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 6.42E-01 p-value: 3.45E-17
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[173]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Crizotinib		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	EGFR tyrosine kinase inhibitor resistance			hsa01521
In-vitro Model	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	NCI-H661	Lung large cell carcinoma	Homo sapiens	CVCL_1577
	NCI-H596	Lung adenosquamous carcinoma	Homo sapiens	CVCL_1571
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H358	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1559
	NCI-H292	Lung mucoepidermoid carcinoma	Homo sapiens	CVCL_0455
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1395	Lung adenocarcinoma	Homo sapiens	CVCL_1467
	EBC-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_2891
	Calu-3	Lung adenocarcinoma	Homo sapiens	CVCL_0609
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	HCC827 (3×10⁶) cells suspended in 100 uL of PBS were injected into the left inguen of female Balb/c nude mice (body weight 18-20 g; age 6 weeks; Beijing Huafukang Bioscience Co., Inc.). When the tumor volumes reached 50-100 mm³ on the 10th posttransplantation day, the mice were randomized into four groups (10 mice per group) and were intragastrically administered vehicle (normal saline), crizotinib (25 mg/kg body weight), chidamide (5 mg/kg), or the combination of the two drugs daily for 21 days. The tumor volumes and body weights of the mice were measured every 3 days.
Response Summary	Chidamide could decrease Hepatocyte growth factor receptor (c-Met/MET) expression by inhibiting mRNA N6-methyladenosine (m6A) modification through the downregulation of METTL3 and WTAP expression, subsequently increasing the crizotinib sensitivity of NSCLC cells in a c-MET-/HGF-dependent manner.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[174]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Responsed Drug	Gefitinib		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vitro Model	NCI-H3255	Lung adenocarcinoma	Homo sapiens	CVCL_6831
Response Summary	METTL3 combines with Hepatocyte growth factor receptor (c-Met/MET) and causes the PI3K/AKT signalling pathway to be manipulated, which affects the sensitivity of lung cancer cells to gefitinib. METTL3 knockdown promotes apoptosis and inhibits proliferation of lung cancer cells.

Melanoma of uvea [ICD-11: 2D0Y]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[175]
Responsed Disease	Melanoma of uvea [ICD-11: 2D0Y]
Target Regulation	Up regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Arrest cell cycle at G1 phase
In-vitro Model	M17 (Neuroblastoma cells)
	M21	Melanoma	Homo sapiens	CVCL_D031
	M23	Cutaneous melanoma	Homo sapiens	CVCL_RT32
	SP-6.5	Uveal melanoma	Homo sapiens	CVCL_7997
Response Summary	METTL3-mediated m6A RNA methylation modulates uveal melanoma cell proliferation, migration, and invasion by targeting Hepatocyte growth factor receptor (c-Met/MET). Cycloleucine (Cyc) was used to block m6 A methylation in UM cells.

High mobility group protein HMG-I/HMG-Y (HMGA1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -8.70E-01 p-value: 2.47E-77
More Results	Click to View More RNA-seq Results

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[176]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Cell Process	mRNA stability
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	FHC	Normal	Homo sapiens	CVCL_3688
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	Groups of HCT116-Luc-shCtrl, HCT116-Luc-shLINC00460, and HCT116-Luc-shLINC00460 + HMGA1 cells (5 × 10⁶) were injected subcutaneously into the flanks of mice correspondingly.
Response Summary	LINC00460 is a novel oncogene of colorectal cancer through interacting with IGF2BP2 and DHX9 and bind to the m6A modified High mobility group protein HMG-I/HMG-Y (HMGA1) mRNA to enhance the HMGA1 mRNA stability. The N6-methyladenosine (m6A) modification of HMGA1 mRNA by METTL3 enhanced HMGA1 expression in CRC.

Histone deacetylase 5 (HDAC5)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -9.48E-01 p-value: 2.87E-28
More Results	Click to View More RNA-seq Results

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[177]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Up regulation
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
In-vivo Model	U2OS cells with stable METTL3 expression were screened using puromycin for subsequent experiments. U2OS cells (1 × 10⁶) were injected subcutaneously to the right side of each mouse (the mice were numbered according to their weight, and the experimenters randomly divided the nude mice into 12 groups by the random number method, with 12 mice in each group). The status of mice was detected every 2 days. Tumor growth and volume were measured once a week.Tumor volume was measured: Volume = Width2 × Length/2. On the 35th day after the operation, nude mice were euthanized by intraperitoneal injection of ≥100 mg/kg pentobarbital sodium. Tumor resection was performed and tumor weight was recorded. Weight loss >10% of the body weight or the maximum diameter of the tumor >1.5 cm was the humane end point.
Response Summary	Higher METTL3 expression indicated poorer prognosis. METTL3 upregulated Histone deacetylase 5 (HDAC5) expression in osteosarcoma cells by increasing the m6A level.

Histone-lysine N-methyltransferase SETD7 (SETD7)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: 7.00E-01 p-value: 6.39E-40
More Results	Click to View More RNA-seq Results

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[178]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Down regulation
Cell Process	Cancer proliferation
	Cancer metastasis
In-vitro Model	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
In-vivo Model	For the subcutaneous implantation model, UM-UC-3 cells (2 × 10⁶ cells per mouse) stably METTL3 knocked down (shMETTL3-1, shMETTL3-2) were injected into the flanks of mice.
Response Summary	METTL3/YTHDF2/Histone-lysine N-methyltransferase SETD7 (SETD7)/KLF4 m6 A axis provide the insight into the underlying mechanism of carcinogenesis and highlight potential therapeutic targets for bladder cancer.

Homeobox protein NANOG (NANOG)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Soma	Mus musculus
Treatment: Mettl3-/- soma Control: Wild type soma		GSE171199
Regulation		logFC: 2.74E+00 p-value: 4.57E-02
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[179]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
Cell Process	Cell migration
	Cell invasion
	Epithelial-mesenchymal transition initiation
Response Summary	In breast cancer, ZNF217 could upregulate Homeobox protein NANOG (NANOG) by reducing N6-methyladenosine levels via methyltransferase-like 13 (METTL3).

Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 1.13E+00 p-value: 4.17E-08
More Results	Click to View More RNA-seq Results

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[180]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Pathway Response	HIF-1 signaling pathway			hsa04066
Pathway Response	Central carbon metabolism in cancer			hsa05230
Cell Process	Glycolysis
Cell Process	Glutaminolysis
In-vitro Model	BEL-7402	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	MHCC97	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4971
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
Response Summary	HBXIP drives metabolic reprogramming in hepatocellular carcinoma cells via METTL3-mediated m6A modification of Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A). Highly expressed HBXIP and METTL3 are associated with dismal oncologic outcomes of patients with hepatocellular carcinoma. The positive relation between HBXIP and METTL3 can activate reprogramming of HCC cell metabolism by inducing m6A modification of HIF-1-alpha, which is unraveled to enhance aggressive biological behaviors of HCC cells.

Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HeLa cell line	Homo sapiens
Treatment: METTL3 knockdown HeLa cells Control: HeLa cells		GSE70061
Regulation		logFC: 3.01E+00 p-value: 5.15E-06
More Results	Click to View More RNA-seq Results

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[4]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Up regulation
Cell Process	Glucose metabolism
Response Summary	AF4/FMR2 family member 4 (AFF4), two key regulators of NF-Kappa-B pathway (Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB) and RELA) and MYC were further identified as direct targets of METTL3-mediated m6A modification.overexpression of METTL3 significantly promoted Bladder cancer cell growth and invasion.

Insulin-like growth factor 1 receptor (IGF1R)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 6.69E-01 p-value: 4.12E-12
More Results	Click to View More RNA-seq Results

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[147]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Up regulation
Cell Process	RNA stability
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
In-vitro Model	LNCaP C4-2B	Prostate carcinoma	Homo sapiens	CVCL_4784
In-vivo Model	At 1 week post-injection with PC-3 cells, mice were randomly assigned to three groups (n = 8 per group): the ASO-NC group (injection with ASO negative control targeting unknown sequence, 5 nmol in 100 uL PBS for each mouse), the ASO-L group (injection with low-dose ASO targeting PCAT6, 5 nmol in 100 uL PBS for each mouse), and the ASO-H group (injection with high-dose ASO targeting PCAT6, 10 nmol in 100 uL PBS for each mouse).
Response Summary	METTL3-mediated m6A modification contributed to PCAT6 upregulation in an IGF2BP2-dependent manner. Furthermore, PCAT6 upregulated Insulin-like growth factor 1 receptor (IGF1R) expression by enhancing IGF1R mRNA stability through the PCAT6/IGF2BP2/IGF1R RNA-protein three-dimensional complex. The m6 A-induced PCAT6/IGF2BP2/IGF1R axis promotes PCa bone metastasis and tumor growth, suggesting that PCAT6 serves as a promising prognostic marker and therapeutic target against bone-metastatic PCa.

Integrin alpha-6 (ITGA6)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shMETTL3 MOLM13 cells Control: MOLM13 cells		GSE98623
Regulation		logFC: -2.38E+00 p-value: 1.75E-72
More Results	Click to View More RNA-seq Results

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[181]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Up regulation
Pathway Response	Cell adhesion molecules			hsa04514
Cell Process	Cell adhesion
	Cell migration
	Cell invasion
In-vitro Model	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
	HEK293T	Normal	Homo sapiens	CVCL_0063
	J82	Bladder carcinoma	Homo sapiens	CVCL_0359
	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
In-vivo Model	For the subcutaneous implantation model, 1 × 10⁷ cells were subcutaneously implanted into 5-week-old BALB/cJNju-Foxn1nu/Nju nude mice.
Response Summary	m6A writer METTL3 and eraser ALKBH5 altered cell adhesion by regulating Integrin alpha-6 (ITGA6) expression in bladder cancer cells. m6A is highly enriched within the ITGA6 transcripts, and increased m6A methylations of the ITGA6 mRNA 3'UTR promotes the translation of ITGA6 mRNA via binding of the m6A readers YTHDF1 and YTHDF3. Inhibition of ITGA6 results in decreased growth and progression of bladder cancer cells in vitro and in vivo.

Integrin beta-1 (ITGB1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -2.05E+00 p-value: 1.83E-215
More Results	Click to View More RNA-seq Results

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[182]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Up regulation
Pathway Response	Cell adhesion molecules			hsa04514
Cell Process	Cell adhesion
In-vitro Model	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
In-vivo Model	All the mice were randomly divided into five groups of four mice each, including PC3-shNC, PC3-shMETTL3-1/2, LNCaP-vector and LNCaP-METTL3 group.
Response Summary	METTL3 regulates the expression of Integrin beta-1 (ITGB1) through m6A-HuR-dependent mechanism, which affects the binding of ITGB1 to Collagen I and tumor cell motility, so as to promote the bone metastasis of prostate cancer.

Intercellular adhesion molecule 1 (ICAM1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: 9.55E-01 p-value: 2.64E-22
More Results	Click to View More RNA-seq Results

Cataract [ICD-11: 9B10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[183]
Responsed Disease	Diabetic cataract [ICD-11: 9B10.21]
Target Regulation	Up regulation
Cell Process	RNA stability
	Cell apoptosis
In-vitro Model	B-3	Normal	Homo sapiens	CVCL_6367
Response Summary	METTL3 modulates the proliferation and apoptosis of lens epithelial cells in diabetic cataract. METTL3 targets the 3' UTR of Intercellular adhesion molecule 1 (ICAM1) to stabilize mRNA stability.

Interferon gamma (IFN-gamma)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Th1 cell line	Mus musculus
Treatment: METTL3 knockout splenic Th1 cells Control: Wild type splenic Th1 cells		GSE129648
Regulation		logFC: -1.72E+00 p-value: 6.66E-03
More Results	Click to View More RNA-seq Results

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[118]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 10⁶ CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of Interferon gamma (IFN-gamma), Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2.

Interferon regulatory factor 1 (Irf1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	ARPE-19 cell line	Homo sapiens
Treatment: shMETTL3 ARPE-19 cells Control: shControl ARPE-19 cells		GSE202017
Regulation		logFC: -9.51E-01 p-value: 1.06E-05
More Results	Click to View More RNA-seq Results

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[118]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 10⁶ CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Interferon regulatory factor 1 (Irf1) mRNA via Ythdf2.

Interferon-induced 54 kDa protein (IFIT2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LNCaP cell line	Homo sapiens
Treatment: shMETTL3 LNCaP cells Control: shControl LNCaP cells		GSE147884
Regulation		logFC: 9.21E-01 p-value: 1.94E-18
More Results	Click to View More RNA-seq Results

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[184]
Responsed Disease	Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
Target Regulation	Down regulation
In-vitro Model	HuCC-T1	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_0324
In-vitro Model	HCCC-9810	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_6908
In-vivo Model	4-week-old female BALB/c nude mice were used for HuCC-T1 tumor xenograft models and 4-week-old female B-NDG mice (Biocytogen, Beijing, China) were used for HCCC-9810 tumor xenograft models. 1 × 10⁷ HuCC-T1 or HCCC-9810 cells were resuspended in 100 ul PBS with Matrigel (1:1), and injected into the right flank of mice (n = 6/group).
Response Summary	METTL3 was upregulated and predicted poor prognosis of patients with intrahepatic cholangiocarcinoma(ICC). H3K4me3 activation-driven METTL3 transcription promotes ICC progression by YTHDF2-mediated Interferon-induced 54 kDa protein (IFIT2) mRNA degradation.

Interferon-inducible protein 4 (ADAR1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	E14.5 LSK cell line	Mus musculus
Treatment: METTL3 knockout E14.5 LSK cells Control: Wild type E14.5 LSK cells		GSE148882
Regulation		logFC: 6.03E-01 p-value: 6.54E-18
More Results	Click to View More RNA-seq Results

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[185]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Pathway Response	RNA degradation			hsa03018
Cell Process	RNA stability
In-vitro Model	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
	U-118MG	Astrocytoma	Homo sapiens	CVCL_0633
	T98G	Glioblastoma	Homo sapiens	CVCL_0556
	A-172	Glioblastoma	Homo sapiens	CVCL_0131
In-vivo Model	2 × 10⁶ U87MG cells already expressing shscr or shADAR1 were subcutaneously injected in the flank of 6-week-old nude mice (nu/nu, Charles River, Wilmington, MA, USA).
Response Summary	METTL3, upregulated in glioblastoma, methylates Interferon-inducible protein 4 (ADAR1) mRNA and increases its protein level leading to a pro-tumorigenic mechanism connecting METTL3, YTHDF1, and ADAR1.

Interleukin enhancer-binding factor 3 (ILF3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HeLa cell line	Homo sapiens
Treatment: METTL3 knockdown HeLa cells Control: HeLa cells		GSE70061
Regulation		logFC: 7.68E-01 p-value: 3.12E-02
More Results	Click to View More RNA-seq Results

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[186]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Approximately 5 × 10⁶ control and ILF3-AS1 silencing Huh7 cells were subcutaneously implanted into the right flank of nude mice.Xenograft size was measured every 7 days and calculated using the equation V(mm³)=(length×width2)/2. 35 days later, the mice were sacrificed, and the tumor tissues were isolated and weighed.
Response Summary	ILF3-AS1 expression was significantly elevated in HCC tissues,mechanistically, ILF3-AS1 associated with Interleukin enhancer-binding factor 3 (ILF3) mRNA and inhibited its degradation. ILF3-AS1 increased ILF3 m6A level via recruiting N6-methyladenosine (m6A) RNA methyltransferase METTL3. Moreover, IFL3-AS1 enhanced the interaction between ILF3 mRNA and m6A reader IGF2BP1.

Interleukin-6 (IL-6)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	ARPE-19 cell line	Homo sapiens
Treatment: shMETTL3 ARPE-19 cells Control: shControl ARPE-19 cells		GSE202017
Regulation		logFC: -1.10E+00 p-value: 7.68E-04
More Results	Click to View More RNA-seq Results

Rheumatoid arthritis [ICD-11: FA20]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[187]
Responsed Disease	Rheumatoid arthritis [ICD-11: FA20]
Target Regulation	Up regulation
Cell Process	Inflammatory response
In-vitro Model	FLS (Rat fibroblast synovial cell line)
In-vivo Model	To establish the adjuvant-induced arthritis (AIA) model, the rats were given complete Freund's adjuvant (CFA; Chondrex, Inc.) on the left paw of 0.1 ml per 100 g of body weight. Additionally, the rats were injected with normal saline to create the negative control (NC) group.
Response Summary	METTL3 knockdown suppressed Interleukin-6 (IL-6), matrix metalloproteinase (MMP)-3, and MMP-9 levels in human RA-FLSs and rat AIA-FLSs.

Intersectin-2 (ITSN2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Pancreatic islets	Mus musculus
Treatment: Mettl3 knockout mice Control: Mettl3 flox/flox mice		GSE155612
Regulation		logFC: 8.48E-01 p-value: 1.42E-04
More Results	Click to View More RNA-seq Results

Ovarian dysfunction [ICD-11: 5A80]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[188]
Responsed Disease	Ovarian dysfunction [ICD-11: 5A80]
Target Regulation	Up regulation
In-vivo Model	All mice described above were maintained on the C57BL/6 J background. Mice lacking Mettl3 in oocytes (referred to as Mettl3^Gdf9 cKO) were generated by crossing Mettl3^flox/flox mice with Gdf9-Cre mice. The Mettl3^flox/flox female mice were used as the control group (referred to as WT). For the fertility test, six pairs of 6 weeks Mettl3^flox/flox and Mettl3^Gdf9 cKO female mice were randomly selected and continually mated to Mettl3^flox/flox male mice which have been confirmed fertility for 5 months. The number of pups and litter size from each female was recorded.
Response Summary	METTL3 targets Intersectin-2 (ITSN2) for m6A modification and then enhances its stability to influence the oocytes meiosis. mRNA m6A modification in follicle development and coordination of RNA stabilization during oocyte growth.

Female infertility [ICD-11: GA31]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[188]
Responsed Disease	Female infertility [ICD-11: GA31]
Target Regulation	Up regulation
In-vivo Model	All mice described above were maintained on the C57BL/6 J background. Mice lacking Mettl3 in oocytes (referred to as Mettl3^Gdf9 cKO) were generated by crossing Mettl3^flox/flox mice with Gdf9-Cre mice. The Mettl3^flox/flox female mice were used as the control group (referred to as WT). For the fertility test, six pairs of 6 weeks Mettl3^flox/flox and Mettl3^Gdf9 cKO female mice were randomly selected and continually mated to Mettl3^flox/flox male mice which have been confirmed fertility for 5 months. The number of pups and litter size from each female was recorded.
Response Summary	METTL3 targets Intersectin-2 (ITSN2) for m6A modification and then enhances its stability to influence the oocytes meiosis. mRNA m6A modification in follicle development and coordination of RNA stabilization during oocyte growth.

Kinesin-like protein KIF3C (KIF3C)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 5.93E-01 p-value: 1.16E-06
More Results	Click to View More RNA-seq Results

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[189]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Up regulation
Cell Process	Cell migration
Cell Process	Cell invasion
In-vitro Model	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	LNCaP C4-2B	Prostate carcinoma	Homo sapiens	CVCL_4784
	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
In-vivo Model	For the proliferation assays, C4-2B cells of KIF3C knockdown, negative control (1×106/200uL) were subcutaneously injected into BALB/c nude mice. The tumors were dissected and weighed (4-6 weeks old, male).
Response Summary	METTL3 induced m6A modification on Kinesin-like protein KIF3C (KIF3C), promoting the stabilization of KIF3C-mRNA by IGF2BP1. KIF3C was overexpressed in prostate cancer, promoting its growth migration and invasion was induced by miR-320d/METTL3 in an m6A dependent process.

Krueppel-like factor 2 (KLF2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -1.15E+00 p-value: 3.23E-14
More Results	Click to View More RNA-seq Results

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[190]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
Response Summary	METTL3 promotes translation of SPHK2 mRNA via an m6A-YTHDF1-dependent manner. Functionally, SPHK2 facilitates GC cell proliferation, migration and invasion by inhibiting Krueppel-like factor 2 (KLF2) expression.

Krueppel-like factor 4 (KLF4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HUVEC cell line	Homo sapiens
Treatment: shMETTL3 HUVEC cells Control: shScramble HUVEC cells		GSE157544
Regulation		logFC: -8.63E-01 p-value: 1.22E-04
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[102]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Down regulation
Pathway Response	TNF signaling pathway			hsa04668
Cell Process	Cell migration
	Cell invasion
	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Response Summary	miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor Krueppel-like factor 4 (KLF4). miR-1915-3p function as a tumor suppressor by targeting SET and has an anti-metastatic therapeutic potential for lung cancer treatment.

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[178]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Down regulation
Cell Process	Cancer proliferation
	Cancer metastasis
In-vitro Model	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
In-vivo Model	For the subcutaneous implantation model, UM-UC-3 cells (2 × 10⁶ cells per mouse) stably METTL3 knocked down (shMETTL3-1, shMETTL3-2) were injected into the flanks of mice.
Response Summary	METTL3/YTHDF2/SETD7/Krueppel-like factor 4 (KLF4) m6 A axis provide the insight into the underlying mechanism of carcinogenesis and highlight potential therapeutic targets for bladder cancer.

Atherosclerosis [ICD-11: BD40]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[85]
Responsed Disease	Atherosclerosis [ICD-11: BD40.Z]
Target Regulation	Down regulation
In-vitro Model	MAEC	Normal	Mus musculus	CVCL_U411
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
Response Summary	In the in vivo atherosclerosis model,partial ligation of the carotid artery led to plaque formation and up-regulation of METTL3 and NLRP1, with down-regulation of KLF4; knockdown of METTL3 via repetitive shRNA administration prevented the atherogenic process, NLRP1 up-regulation, and Krueppel-like factor 4 (KLF4) down-regulation. Collectively, it has demonstrated that METTL3 serves a central role in the atherogenesis induced by oscillatory stress and disturbed blood flow.

Lymphoid enhancer-binding factor 1 (LEF1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: 6.28E-01 p-value: 2.52E-06
More Results	Click to View More RNA-seq Results

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[191]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	NHOst (Normal human osteoblast cells)
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
In-vivo Model	The Metastatic Bone Tumor Model was established via injecting HOS cells into the right tibia of each animal.
Response Summary	METTL3 silence decreased the m6A methylation and total mRNA level of Lymphoid enhancer-binding factor 1 (LEF1),the m6A methyltransferase METTL3 promotes osteosarcoma cell progression by regulating the m6A level of LEF1 and activating Wnt/beta-catenin signaling pathway.

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[192]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Cell activity and migratory
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
Response Summary	METTL3 influences the activity of the Wnt pathway through m6A methylation on Lymphoid enhancer-binding factor 1 (LEF1) mRNA, thereafter, promoting the progression of prostate cancer.

M-phase inducer phosphatase 2 (CDC25B)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HeLa cell line	Homo sapiens
Treatment: METTL3 knockdown HeLa cells Control: HeLa cells		GSE70061
Regulation		logFC: 2.72E+00 p-value: 5.89E-03
More Results	Click to View More RNA-seq Results

Head and neck squamous carcinoma [ICD-11: 2B6E]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[193]
Responsed Disease	Head and neck squamous carcinoma [ICD-11: 2B6E]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	Tu 686	Laryngeal squamous cell carcinoma	Homo sapiens	CVCL_4916
	Tu 212	Head and neck squamous cell carcinoma	Homo sapiens	CVCL_4915
	SAS	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1675
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	HEp-2	Endocervical adenocarcinoma	Homo sapiens	CVCL_1906
	FaDu	Hypopharyngeal squamous cell carcinoma	Homo sapiens	CVCL_1218
In-vivo Model	Tumour xenograft models were established in nude mice bearing: SAS cells cells stably transfected with METTL3-shRNA and the corresponding control vector. The different HNSCC cells (5 × 10⁶) were subcutaneously injected into the right axilla of nude mice (n = 6 per group).
Response Summary	METTL3 enhanced the m6A modification of M-phase inducer phosphatase 2 (CDC25B) mRNA, which maintained its stability and upregulated its expression, thereby activating G2/M phase of cell cycle and leading to HNSCC malignant progression.

Macrophage metalloelastase (MMP12)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Raw 264.7 cell line	Mus musculus
Treatment: METTL3 knockout Raw 264.7 cells Control: Wild type Raw 264.7 cells		GSE162248
Regulation		logFC: -3.62E+00 p-value: 1.51E-23
More Results	Click to View More RNA-seq Results

Emphysema [ICD-11: CA21]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[160]
Responsed Disease	Emphysema [ICD-11: CA21]
Target Regulation	Down regulation
Pathway Response	MAPK signaling pathway	hsa04010
Response Summary	METTL3-mediated formation of EV miR-93, facilitated by m6A, is implicated in the aberrant cross-talk of epithelium-macrophages, indicating that this process is involved in the smoking-related emphysema. EV miR-93 was used as a novel risk biomarker for CS-induced emphysema. MiR-93 activated the JNK pathway by targeting dual-specificity phosphatase 2 (DUSP2), which elevated the levels of matrix metalloproteinase 9 (MMP9) and Macrophage metalloelastase (MMP12) and induced elastin degradation, leading to emphysema.

Matrix metalloproteinase-9 (MMP9)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 2.14E+00 p-value: 4.12E-24
More Results	Click to View More RNA-seq Results

Emphysema [ICD-11: CA21]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[160]
Responsed Disease	Emphysema [ICD-11: CA21]
Target Regulation	Down regulation
Pathway Response	MAPK signaling pathway	hsa04010
Response Summary	METTL3-mediated formation of EV miR-93, facilitated by m6A, is implicated in the aberrant cross-talk of epithelium-macrophages, indicating that this process is involved in the smoking-related emphysema. EV miR-93 was used as a novel risk biomarker for CS-induced emphysema. MiR-93 activated the JNK pathway by targeting dual-specificity phosphatase 2 (DUSP2), which elevated the levels of Matrix metalloproteinase-9 (MMP9) and matrix metalloproteinase 12 (MMP12) and induced elastin degradation, leading to emphysema.

Rheumatoid arthritis [ICD-11: FA20]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[187]
Responsed Disease	Rheumatoid arthritis [ICD-11: FA20]
Target Regulation	Up regulation
Cell Process	Inflammatory response
In-vitro Model	FLS (Rat fibroblast synovial cell line)
In-vivo Model	To establish the adjuvant-induced arthritis (AIA) model, the rats were given complete Freund's adjuvant (CFA; Chondrex, Inc.) on the left paw of 0.1 ml per 100 g of body weight. Additionally, the rats were injected with normal saline to create the negative control (NC) group.
Response Summary	METTL3 knockdown suppressed interleukin (IL)-6, matrix metalloproteinase (MMP)-3, and Matrix metalloproteinase-9 (MMP9) levels in human RA-FLSs and rat AIA-FLSs.

Meltrin-beta (ADAM19)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HUVEC cell line	Homo sapiens
Treatment: shMETTL3 HUVEC cells Control: shScramble HUVEC cells		GSE157544
Regulation		logFC: -7.06E-01 p-value: 4.35E-03
More Results	Click to View More RNA-seq Results

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[194]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Target Regulation	Down regulation
Cell Process	Cells growth
	Cells self-renewal
	Tumorigenesis
	MicroRNAs in cancer (hsa05206)
In-vitro Model	GSC	Glioma	Epinephelus akaara	CVCL_M752
In-vivo Model	2 × 10⁵ dissociated cells in 2 uL PBS were injected into the following site (anteroposterior [AP] +0.6 mm, mediolateral [ML] +1.6 mm, and dorsoventricular [DV] 2.6 mm) with a rate of 1 uL/min.
Response Summary	Knockdown of METTL3 or METTL14 induced changes in mRNA m6A enrichment and altered mRNA expression of genes (e.g., Meltrin-beta (ADAM19)) with critical biological functions in GSCs. Treatment with MA2, a chemical inhibitor of FTO, dramatically suppressed GSC-induced tumorigenesis and prolonged lifespan in GSC-grafted animals.

Metalloreductase STEAP2 (STEAP2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	ARPE-19 cell line	Homo sapiens
Treatment: shMETTL3 ARPE-19 cells Control: shControl ARPE-19 cells		GSE202017
Regulation		logFC: 6.65E-01 p-value: 3.16E-05
More Results	Click to View More RNA-seq Results

Thyroid Cancer [ICD-11: 2D10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[195]
Responsed Disease	Papillary thyroid cancer [ICD-11: 2D10.1]
Target Regulation	Up regulation
Pathway Response	Hedgehog signaling pathway			hsa04340
Cell Process	Epithelial-to-mesenchymal transition
	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	TPC-1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
	KTC-1	Thyroid carcinoma	Homo sapiens	CVCL_6300
	B-CPAP	Thyroid gland carcinoma	Homo sapiens	CVCL_0153
In-vivo Model	BCPAP cells (5×10⁶) were introduced into the mice by means of subcutaneous injection through the flank area. STEAP2-saRNA or NC-saRNA (n = 6 for each group) was given by intratumoral multipoint injection at an interval of 3 days (5 injections in total) using an in vivo transfection reagent (Entranster -in vivo, Engreen, China) as per the vendor-provided protocol. Tumor volume (V) was monitored and calculated as follows: V = (L×W2)/2. For the in vivo tumor metastasis assay, BCPAP cells (5×10⁶ cells) were administrated into mice through the tail vein. STEAP2-saRNA or NC-saRNA (n = 6 for each group) was given via tail vein injection at an interval of 3 days (8 injections in total).
Response Summary	Metalloreductase STEAP2 (STEAP2) overexpression inhibited papillary thyroid cancer cell proliferation, migration, and invasion in vitro and inhibited lung metastasis and tumorigenicity in vivo. METTL3 stabilized STEAP2 mRNA and regulated STEAP2 expression positively in an m6A-dependent manner.

Microprocessor complex subunit DGCR8 (DGCR8)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Liver	Mus musculus
Treatment: Mettl3 knockout liver Control: Wild type liver cells		GSE198513
Regulation		logFC: -9.09E-01 p-value: 2.99E-21
More Results	Click to View More RNA-seq Results

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[196]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	UP regulation
In-vitro Model	WPMY-1	Normal	Homo sapiens	CVCL_3814
	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
Response Summary	METTL3 promoted cell proliferation, migration, invasion and tumorigenesis in PCa. METTL3 upregulating the level of m6A, and interacted with Microprocessor complex subunit DGCR8 (DGCR8) to recognize the m6A modification of pre-miR-182 to regulate its splicing and maturation and promote the high expression of miRNA.

Oral cavity/oesophagus/stomach in situ carcinoma [ICD-11: 2E60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[197]
Responsed Disease	Esophageal squamous cell carcinoma [ICD-11: 2B70.1]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Epithelial-mesenchymal transition
In-vitro Model	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
	KYSE-30	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1351
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
	HET-1A	Normal	Homo sapiens	CVCL_3702
	CVCL_E307	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_E307
	Eca-109	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
In-vivo Model	Luciferase-labeled KYSE150 cells (5 × 10⁶) were inoculated into the footpads of BALB/c nude mice (4-5 weeks old, 18-20 g) to establish the popliteal lymphatic metastasis model.
Response Summary	METTL3 could interact with Microprocessor complex subunit DGCR8 (DGCR8) protein and positively modulate pri-miR-320b maturation process in an N6-methyladenosine (m6A)-dependent manner. Therefore, our findings uncover a VEGF-C-independent mechanism of exosomal and intracellular miR-320b-mediated LN metastasis and identify miR-320b as a novel predictive marker and therapeutic target for LN metastasis in ESCC.

Chondropathies [ICD-11: FB82]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[198]
Responsed Disease	Chondropathies [ICD-11: FB82]
Target Regulation	Up regulation
Cell Process	RNA mature
In-vitro Model	Cartilage cells (From the cartilage tissue samples from patients)
Response Summary	Interleukin 1-beta (IL-1-beta) is an important inducer of cartilage degeneration that can induce an inflammatory cascade reaction in chondrocytes and inhibit the normal biological function of cells. METTL3 could regulate miR-126-5p maturation, we first confirmed that METTL3 can bind the key protein underlying pri-miRNA processing, Microprocessor complex subunit DGCR8 (DGCR8). Additionally, when METTL3 expression was inhibited, the miR-126-5p maturation process was blocked.

Mothers against decapentaplegic homolog 3 (SMAD3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 1.25E+00 p-value: 1.46E-105
More Results	Click to View More RNA-seq Results

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[124]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell invasion
	Cell migration
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In-vivo Model	BALB/c nude mice (4 weeks old) were acquired from Vital River Laboratory (Beijing, China). HCT116 cells with stable circ1662 expression (2 × 10⁶ in 100 L of PBS) were injected via the tail vein. After 45 days, the mice were sacrificed. The lung metastatic carcinoma specimens were processed into paraffin-embedded sections for subsequent H&E staining and IHC.
Response Summary	METTL3-induced circ1662 promoted colorectal cancer cell invasion and migration by accelerating YAP1 nuclear transport. Circ1662 enhanced CRC invasion and migration depending on YAP1 and Mothers against decapentaplegic homolog 3 (SMAD3). This result implies that circ1662 is a new prognostic and therapeutic marker for CRC metastasis.

Mothers against decapentaplegic homolog 7 (SMAD7)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -6.27E-01 p-value: 8.80E-36
More Results	Click to View More RNA-seq Results

Inflammatory response [ICD-11: MG46]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[162]
Responsed Disease	Inflammatory response [ICD-11: MG46]
Target Regulation	Down regulation
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	RNA stability
In-vitro Model	MC3T3-E1	Normal	Mus musculus	CVCL_0409
Response Summary	METTL3 knockdown inhibits osteoblast differentiation and Smad-dependent signaling by stabilizing Mothers against decapentaplegic homolog 7 (SMAD7) and Smurf1 mRNA transcripts via YTHDF2 involvement and activates the inflammatory response by regulating MAPK signaling in LPS-induced inflammation.

NACHT/LRR/PYD domains-containing protein 1 (NLRP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HUVEC cell line	Homo sapiens
Treatment: shMETTL3 HUVEC cells Control: shScramble HUVEC cells		GSE157544
Regulation		logFC: -7.83E-01 p-value: 2.96E-03
More Results	Click to View More RNA-seq Results

Atherosclerosis [ICD-11: BD40]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[85]
Responsed Disease	Atherosclerosis [ICD-11: BD40.Z]
Target Regulation	Up regulation
In-vitro Model	MAEC	Normal	Mus musculus	CVCL_U411
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
Response Summary	In the in vivo atherosclerosis model,partial ligation of the carotid artery led to plaque formation and up-regulation of METTL3 and NACHT/LRR/PYD domains-containing protein 1 (NLRP1), with down-regulation of KLF4; knockdown of METTL3 via repetitive shRNA administration prevented the atherogenic process, NLRP3 up-regulation, and KLF4 down-regulation. Collectively, it has demonstrated that METTL3 serves a central role in the atherogenesis induced by oscillatory stress and disturbed blood flow.

NAD-dependent protein deacetylase sirtuin-1 (SIRT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Embryonic stem cells	Mus musculus
Treatment: METTL3 knockout mESCs Control: Wild type mESCs		GSE156481
Regulation		logFC: -7.40E-01 p-value: 1.00E-18
More Results	Click to View More RNA-seq Results

Type 2 diabetes mellitus [ICD-11: 5A11]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[48]
Responsed Disease	Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulation	Up regulation
Pathway Response	Insulin resistance			hsa04931
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3^fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3^fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3^fl/fl) were used for experiments.
Response Summary	Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. The expression of Acc1, Acly, Dgat2, Ehhadh, Fasn, Foxo, Pgc1a and NAD-dependent protein deacetylase sirtuin-1 (SIRT1), which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.

Osteoarthritis [ICD-11: FA05]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[199]
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulation	Up regulation
In-vitro Model	Chondrocytes (Chondrocytes were isolated from human cartilage and cultured)
Response Summary	m6A-mediated LINC00680 regulates the proliferation and ECM degradation of chondrocytes through LINC00680/m6A/NAD-dependent protein deacetylase sirtuin-1 (SIRT1) mRNA axis. METTL3-mediated LINC00680 accelerates osteoarthritis(OA) progression, which provides novel understanding of the role of m6A and lncRNA in OA.

Neurogenic locus notch homolog protein 1 (NOTCH1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -6.68E-01 p-value: 1.32E-12
More Results	Click to View More RNA-seq Results

Oral cavity/oesophagus/stomach in situ carcinoma [ICD-11: 2E60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[200]
Responsed Disease	Esophageal squamous cell carcinoma [ICD-11: 2B70.1]
Target Regulation	Up regulation
Pathway Response	Notch signaling pathway			hsa04330
Cell Process	Cell migration
	Cell invasion
In-vitro Model	TE-9	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1767
	KYSE-30	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1351
In-vivo Model	For induction of ESCC, 4-week-old mice were treated with drinking water containing 50 ug/mL 4NQO (Sigma-Aldrich, USA) for 16 weeks and then given normal drinking water for another 4-5 weeks. Cre was activated by the intraperitoneal injection of tamoxifen (Sigma-Aldrich, USA) at a dose of 9 mg per 40 g body weight every other day for a total of three injections. For tumor measurement, mice were sacrificed, and the esophagus was dissected immediately. The surface areas of tumors were measured as described previously.
Response Summary	METTL3-catalyzed m6A modification promotes Neurogenic locus notch homolog protein 1 (NOTCH1) expression and the activation of the Notch signaling pathway. Forced activation of Notch signaling pathway successfully rescues the growth, migration, and invasion capacities of METTL3-depleted ESCC cells.

Neurogenic locus notch homolog protein 2 (NOTCH2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 1.84E+00 p-value: 2.61E-238
More Results	Click to View More RNA-seq Results

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[201]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Responsed Drug	Melittin		Investigative	Drug Info
Target Regulation	Down regulation
Cell Process	miRNA maturation
	Cell apoptosis
In-vitro Model	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	EJ (Human bladder cancer cells)
	BIU-87	Human bladder cancer cells	Homo sapiens	CVCL_6881
In-vivo Model	For melittin treatment study, 4-week-old female BALB/c nude mice were subcutaneously injected with 1 × 10⁷ T24 or BIU87 cells.
Response Summary	METTL3 acts as a fate determinant that controls the sensitivity of bladder cancer cells to melittin treatment. Moreover, METTL3/miR-146a-5p/NUMB/Neurogenic locus notch homolog protein 2 (NOTCH2) axis plays an oncogenic role in bladder cancer pathogenesis and could be a potential therapeutic target for recurrent bladder cancer treatment.

Nuclear factor erythroid 2-related factor 2 (NFE2L2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -1.10E+00 p-value: 4.72E-06
More Results	Click to View More RNA-seq Results

Diseases of the urinary system [ICD-11: GC2Z]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[65]
Responsed Disease	Diseases of the urinary system [ICD-11: GC2Z]
Responsed Drug	Colistin	Approved	Drug Info
Target Regulation	Up regulation
Cell Process	Oxidative stress
	Cell apoptosis
In-vivo Model	The 60 female Kunming mice were divided into two groups (n = 30): control group (injection of physiological saline through the caudal vein) and colistin group (injection of 15 mg/kg colistin, twice a day, with an eight-hour interval).
Response Summary	m6A methylation was involved in oxidative stress-mediated apoptosis in the mechanism of colistin nephrotoxicity. METTL3-mediated M6A methylation modification is involved in colistin-induced nephrotoxicity through apoptosis mediated by Keap1/Nuclear factor erythroid 2-related factor 2 (NFE2L2) signaling pathway.

Nuclear factor NF-kappa-B p105 subunit (NF-Kappa-B/NFKB1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -6.78E-01 p-value: 1.44E-07
More Results	Click to View More RNA-seq Results

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[202]
Responsed Disease	Glioma [ICD-11: 2A00.0]
Target Regulation	Up regulation
Pathway Response	NF-kappa B signaling pathway			hsa04064
In-vitro Model	U87 (A primary glioblastoma cell line)
	N33 (The GBM patient-derived cell line)
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	H4	Astrocytoma	Homo sapiens	CVCL_1239
In-vivo Model	Five-week-old female BALB/c nude mice (Charles Rivers, Beijing, China) were selected for the experiments. U87 cells (5 × 10⁵) transfected with an empty vector, YTHDF2 overexpression, or METTL3 overexpression vectors were suspended in PBS and injected into the right frontal node of nude mice. The inoculation position was 2 mm lateral and 2 mm posterior to the anterior fontanel. Tumor size was estimated from luciferase volume measurements and MRI. The mice were sacrificed when they exhibited disturbed activity or convulsion. The brain was then harvested and embedded in paraffin.
Response Summary	YTHDF2 accelerated UBXN1 mRNA degradation via METTL3-mediated m6A, which, in turn, promoted Nuclear factor NF-kappa-B p105 subunit (NF-Kappa-B/NFKB1) activation. YTHDF2 promotes the malignant progression of gliomas and revealed important insight into the upstream regulatory mechanism of NF-Kappa-B activation via UBXN1 with a primary focus on m6A modification.

Obesity [ICD-11: 5B81]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[110]
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway	hsa04150
	HIF-1 signaling pathway	hsa04066
In-vivo Model	The 8-10 weeks old mice were fed either a high fat diet or HF-CDAA , ad lib for 6-12 weeks. Chow diet was used as control for HFD.The mouse liver was perfused with PBS through portal vein, and liver tissue was cut into small pieces by a scissor. The single cell was made using syringe plunger to mull the tissue, and passed through a 40 uM cell strainer.
Response Summary	The contribution of METTL3-mediated m6A modif ication of Ddit4 mRNA to macrophage metabolic reprogramming in non-alcoholic fatty liver disease and obesity. In METTL3-deficient macrophages, there is a significant downregulation of mammalian target of rapamycin (mTOR) and Nuclear factor NF-kappa-B p105 subunit (NF-Kappa-B/NFKB1) pathway activity in response to cellular stress and cytokine stimulation, which can be restored by knockdown of DDIT4.

Non-alcoholic fatty liver disease [ICD-11: DB92]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[203]
Responsed Disease	Nonalcoholic steatohepatitis [ICD-11: DB92.1]
Target Regulation	Up regulation
In-vitro Model	KCs (Mouse Kupffer cells (BeNa Culture Collection, Beijing, China; BNCC340733))
In-vivo Model	At 8 weeks of age, METTL14 cKO and WT mice were challenged with LPS (Sigma-Aldrich, St. Louis, MO; L2880, single intraperitoneal injection at 5 mg/kg, n = 3) or CCl4 (10%, Macklin, Shanghai, China; C805332, intraperitoneal injection at 5 mL/kg diluted with corn oil, twice per week for 4 weeks, n = 3). The corresponding control groups were treated with single intraperitoneal injection of saline (n = 3) or intraperitoneal injection of corn oil twice per week for 4 weeks (n = 3), respectively. Two hours after LPS injection and 4 weeks after CCl4 treatment, METTL14 cKO and WT mice were etherized and the primary KCs were isolated from liver according to a previously published method.
Response Summary	Nuclear factor NF-kappa-B p105 subunit (NF-Kappa-B/NFKB1) acts as transcription factor to transactivate METTL3/METTL14 genes upon LPS challenge, leading to global RNA m6A hypermethylation. m6A modification in TGF-beta1 upregulation, which helps to shed light on the molecular mechanism of nonalcoholic steatohepatitis(NASH) progression.

Nucleobindin-1 (NUCB1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	DKO-1 cell line	Homo sapiens
Treatment: METTL3 knockdown DKO-1 cell Control: DKO-1 cell		GSE182382
Regulation		logFC: -7.45E-01 p-value: 2.41E-03
More Results	Click to View More RNA-seq Results

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[204]
Responsed Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Responsed Drug	Gemcitabine		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cell proliferation
Cell Process	Cell autophagy
In-vitro Model	SW1990	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	HEK293T	Normal	Homo sapiens	CVCL_0063
	CFPAC-1	Cystic fibrosis	Homo sapiens	CVCL_1119
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
In-vivo Model	5 × 10⁶ SW1990 cells expressing NUCB1 (oeNUCB1) or control vector (oeNC) were injected subcutaneously.
Response Summary	METTL3-mediated m6A modification on Nucleobindin-1 (NUCB1) 5'UTR via the reader YTHDF2 as a mechanism for NUCB1 downregulation in PDAC. This study revealed crucial functions of NUCB1 in suppressing proliferation and enhancing the effects of gemcitabine in pancreatic cancer cells.

Nucleolar protein 3 (ARC)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Embryonic stem cells	Mus musculus
Treatment: METTL3 knockout ESCs Control: Wild type ESCs		GSE146466
Regulation		logFC: 1.50E+00 p-value: 1.12E-06
More Results	Click to View More RNA-seq Results

Alzheimer disease [ICD-11: 8A20]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[205]
Responsed Disease	Alzheimer disease [ICD-11: 8A20]
Target Regulation	Up regulation
In-vitro Model	SH-SY5Y	Neuroblastoma	Homo sapiens	CVCL_0019
Response Summary	METTL3 rescues the A-Bete-induced reduction of Nucleolar protein 3 (ARC) expression via YTHDF1-Dependent m6A modification, which suggests an important mechanism of epigenetic alteration in AD.

Oxidative stress-induced growth inhibitor 1 (OSGIN1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Liver	Mus musculus
Treatment: Mettl3 knockout liver Control: Wild type liver cells		GSE198513
Regulation		logFC: -1.34E+00 p-value: 4.00E-87
More Results	Click to View More RNA-seq Results

Trachea cancer [ICD-11: 2C24]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[206]
Responsed Disease	Trachea cancer [ICD-11: 2C24]
Target Regulation	Up regulation
Cell Process	Cell injury
	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	HBE (Human bronchial epithelial cell line)
Response Summary	METTL3 regulates PM 2.5-induced cell injury by targeting Oxidative stress-induced growth inhibitor 1 (OSGIN1) in human airway epithelial cells.

PI3-kinase subunit alpha (PI3k/PIK3CA)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HULEC-5a cell line	Homo sapiens
Treatment: METTL3 knockdown HULEC-5a cells Control: HULEC-5a cells		GSE200649
Regulation		logFC: -2.36E+00 p-value: 7.04E-03
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[207]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
Response Summary	miR-600 inhibited lung cancer via down-regulating METTL3 expression, and knockdown of METTL3 was used as a novel strategy for lung cancer therapy. The PI3-kinase subunit alpha (PI3k/PIK3CA)/Akt pathway is implicated in cell growth and survival and we also observed that knockdown of METTL3 changed the expression and phosphorylation of proteins of PI3K signaling pathway members.

Renal cell carcinoma [ICD-11: 2C90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[109]
Responsed Disease	Renal cell carcinoma [ICD-11: 2C90]
Target Regulation	Down regulation
Cell Process	Epithelial-to-mesenchymal transition
Cell Process	Arrest cell cycle at G0/G1 phase
In-vitro Model	ACHN	Papillary renal cell carcinoma	Homo sapiens	CVCL_1067
	Caki-1	Clear cell renal cell carcinoma	Homo sapiens	CVCL_0234
	Caki-2	Papillary renal cell carcinoma	Homo sapiens	CVCL_0235
	HK2	Normal	Acipenser baerii	CVCL_YE28
In-vivo Model	Cells (5×10⁶ cells in 200 uL) were suspended with 100 uL PBS and 100 uL Matrigel Matrix, and injected subcutaneously into the left armpit of each mouse.
Response Summary	Knockdown of METTL3 could obviously promote cell proliferation, migration and invasion function, and induce G0/G1 arrest,METTL3 acts as a novel marker for tumorigenesis, development and survival of RCC. Knockdown of METTL3 promoted changes in PI3-kinase subunit alpha (PI3k/PIK3CA)/AKT/mTOR markers' expression with a gain in p-PI3k, p-AKT, p-mTOR and p-p70, and a loss of p-4EBP1.

Poly [ADP-ribose] polymerase 1 (PARP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shMETTL3 MOLM13 cells Control: MOLM13 cells		GSE98623
Regulation		logFC: 1.69E+00 p-value: 1.05E-54
More Results	Click to View More RNA-seq Results

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[208]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Responsed Drug	Oxaliplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
	Signaling pathways regulating pluripotency of stem cells			hsa04550
Cell Process	RNA stability
	Excision repair
In-vitro Model	SNU-719	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_5086
	MKN74	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_2791
	HEK293T	Normal	Homo sapiens	CVCL_0063
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
In-vivo Model	100,000 pLKO and PARP1-sh1 (PT1 and PT2) cells were mixed with matrix gel and inoculate into BALB/C nude mice, respectively. After 25 days, 6 organoid transplanted tumor mice were treated with oxaliplatin (Sellekchem, s1224) twice a week for 4 weeks at a dose of 5 mg/kg.
Response Summary	m6A methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting Poly [ADP-ribose] polymerase 1 (PARP1) mRNA stability which increases base excision repair pathway activity. METTTL3 enhances the stability of PARP1 by recruiting YTHDF1 to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA.

Polycomb complex protein BMI-1 (BMI1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Pancreatic islets	Mus musculus
Treatment: Mettl3 knockout mice Control: Mettl3 flox/flox mice		GSE155612
Regulation		logFC: 5.95E-01 p-value: 1.91E-03
More Results	Click to View More RNA-seq Results

Head and neck squamous carcinoma [ICD-11: 2B6E]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[209]
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulation	Up regulation
In-vitro Model	UM1	Tongue squamous cell carcinoma	Homo sapiens	CVCL_VH00
	SCC-9	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1685
	SCC-25	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1682
	SCC-15	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1681
	HSC-3	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1288
	HOK	Normal	Hexagrammos otakii	CVCL_YE19
In-vivo Model	To construct the subcutaneous tumorigenesis model, the cells were suspended in 100 uL of PBS and Matrigel matrix (BD Biosciences, USA) (1:1) and injected into the right flanks of 6-week-old female BALB/c nude mice.To construct the lymph node metastasis model, we injected 1 × 10⁵/50 uL stably infected SCC9 cells into the left hind footpads of BALB/c mice.
Response Summary	METTL3 promotes Polycomb complex protein BMI-1 (BMI1) translation in OSCC under the cooperation with m6A reader IGF2BP1. And the study revealed that METTL3 promotes OSCC proliferation and metastasis through BMI1 m6A methylation.

PPAR-gamma coactivator 1-alpha (PGC-1a/PPARGC1A)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shMETTL3 MOLM13 cells Control: MOLM13 cells		GSE98623
Regulation		logFC: -3.59E+00 p-value: 8.55E-10
More Results	Click to View More RNA-seq Results

Type 2 diabetes mellitus [ICD-11: 5A11]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[48]
Responsed Disease	Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulation	Up regulation
Pathway Response	Insulin resistance			hsa04931
Cell Process	Lipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3^fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3^fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3^fl/fl) were used for experiments.
Response Summary	Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. The expression of Acc1, Acly, Dgat2, Ehhadh, Fasn, Foxo, PPAR-gamma coactivator 1-alpha (PGC-1a/PPARGC1A) and Sirt1, which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.

PR domain zinc finger protein 2 (PRDM2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Pancreatic islets	Mus musculus
Treatment: Mettl3 knockout mice Control: Mettl3 flox/flox mice		GSE155612
Regulation		logFC: 1.05E+00 p-value: 2.68E-04
More Results	Click to View More RNA-seq Results

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[27]
Responsed Disease	Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Responsed Drug	Arsenite		Phase 2	Drug Info
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
In-vitro Model	HaCaT	Normal	Homo sapiens	CVCL_0038
Response Summary	METTL3 significantly decreased m6A level, restoring p53 activation and inhibiting cellular transformation phenotypes in the arsenite-transformed cells. m6A downregulated the expression of the positive p53 regulator, PR domain zinc finger protein 2 (PRDM2), through the YTHDF2-promoted decay of PRDM2 mRNAs. m6A upregulated the expression of the negative p53 regulator, YY1 and MDM2 through YTHDF1-stimulated translation of YY1 and MDM2 mRNA. This study further sheds light on the mechanisms of arsenic carcinogenesis via RNA epigenetics.

Prominin-1 (CD133)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -7.09E-01 p-value: 5.71E-66
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[122]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
Response Summary	Knockdown of METTL3 downregulated protein levels of SOX2, Prominin-1 (CD133) and CD44 in MCF-7 cells. METTL3 is upregulated in breast cancer, and it promotes the stemness and malignant progression of BCa through mediating m6A modification on SOX2 mRNA.

Prostaglandin G/H synthase 2 (Coll X/PTGS2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shMETTL3 MOLM13 cells Control: MOLM13 cells		GSE98623
Regulation		logFC: -2.16E+00 p-value: 5.15E-154
More Results	Click to View More RNA-seq Results

Osteoarthritis [ICD-11: FA05]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[32]
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulation	Up regulation
Cell Process	Inflammatory response and apoptosis
In-vitro Model	ATDC-5	Mouse teratocarcinoma	Mus musculus	CVCL_3894
In-vivo Model	The right knee joint of each OA mouse was injected with 1U of type VII collagenase over two consecutive days to obtain experimental OA joint, and the control mice received the equal volume of physiological saline.
Response Summary	METTL3 has a functional role in mediates osteoarthritis progression by regulating NF-Kappa-B signaling and ECM synthesis in chondrocytes that shed insight on developing preventive and curative strategies for OA by focusing on METTL3 and mRNA methylation. Silencing of METTL3 promotes degradation of extracellular matrix (ECM) by reducing the expression of MMP-13 and Prostaglandin G/H synthase 2 (Coll X/PTGS2), elevating the expression of Aggrecan and Coll II.

Protein AATF (AATF/CHE1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Liver	Mus musculus
Treatment: Mettl3 knockout liver Control: Wild type liver cells		GSE198513
Regulation		logFC: -6.23E-01 p-value: 2.02E-10
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[22]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulation	Up regulation
Cell Process	Cell growth and death
	Cell apoptosis
In-vitro Model	ADR-resistant MCF-7 (MCF-7/ADR) cells (Human breast cancer doxorubicin-resistant cell line)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
In-vivo Model	Cell suspensions (2 × 10⁶ cells/mL) made with MCF-7/ADR cells stably expressing METTL3 and/or miR-221-3p inhibitor were subcutaneously implanted into each mouse. One week later, xenografted mice were injected with 0.1 mL ADR (25 mg/kg, intraperitoneal injection) twice a week.
Response Summary	METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating pri-microRNA-221-3p maturation in a m6A-dependent manner. METTL3 knockdown was shown to reduce the expression of miR-221-3p by reducing pri-miR-221-3p m6A mRNA methylation, reducing the expression of MDR1 and BCRP, and inducing apoptosis. Identified the METTL3/miR-221-3p/HIPK2/Protein AATF (AATF/CHE1) axis as a novel signaling event that will be responsible for resistance of BC cells to ADR.

Protein kinase C eta type (PKC-eta)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: 8.88E-01 p-value: 2.37E-29
More Results	Click to View More RNA-seq Results

Diseases of arteries or arterioles [ICD-11: BD5Y]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[96]
Responsed Disease	Diseases of arteries or arterioles [ICD-11: BD5Y]
Target Regulation	Down regulation
In-vitro Model	ACBRI-183 (Human retinal pericytes (ACBRI-183) was obtained from Cell Systems Corp. (CSC, USA))
In-vivo Model	Mettl3 floxed mice were purchased from GemPharmatech Co. Ltd (Nanjing, China). Pdgfr-Beta-Cre mice were purchased from Beijing Biocytogen Co. Ltd (Beijing, China) generated on C57BL/6J background. Mettl3 ^flox/flox mice were crossed with Pdgfr-Beta-Cre mice to generate pericyte-specific Mettl3 knockout mice. All mice were bred under the specific-pathogen free condition with free access to diet and water or their nursing mothers with alternating 12/12 light-dark cycle (lights on at 08:00 and off at 20:00).
Response Summary	Specific depletion of METTL3 in pericytes suppressed diabetes-induced pericyte dysfunction and Microvascular complication in vivo. METTL3 overexpression impaired pericyte function by repressing Protein kinase C eta type (PKC-eta), FAT4, and PDGFRA expression, which was mediated by YTHDF2-dependent mRNA decay.

Protein numb homolog (NUMB)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: METTL3 knockdown MDA-MB-231 cells Control: MDA-MB-231 cells		GSE70061
Regulation		logFC: 9.75E-01 p-value: 1.24E-03
More Results	Click to View More RNA-seq Results

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[201]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Responsed Drug	Melittin		Investigative	Drug Info
Target Regulation	Down regulation
Cell Process	miRNA maturation
	Cell apoptosis
In-vitro Model	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	EJ (Human bladder cancer cells)
	BIU-87	Human bladder cancer cells	Homo sapiens	CVCL_6881
In-vivo Model	For melittin treatment study, 4-week-old female BALB/c nude mice were subcutaneously injected with 1 × 10⁷ T24 or BIU87 cells.
Response Summary	METTL3 acts as a fate determinant that controls the sensitivity of bladder cancer cells to melittin treatment. Moreover, METTL3/miR-146a-5p/Protein numb homolog (NUMB)/NOTCH2 axis plays an oncogenic role in bladder cancer pathogenesis and could be a potential therapeutic target for recurrent bladder cancer treatment.

Protein yippee-like 5 (YPEL5)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -6.48E-01 p-value: 2.75E-26
More Results	Click to View More RNA-seq Results

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[210]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	NCM460	Normal	Homo sapiens	CVCL_0460
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vivo Model	For the xenograft model, METTL3 stable overexpressed SW620 cells (1 × 10⁷) or control cells were subcutaneously injected into the right axilla of the female anesthetized BALB/C nude mice (4-6 weeks old, 18-20 g, four mice per group), respectively. The body weight and tumor volumes (length × width2 × 0.5) were measured twice a week. After 21 days, all mice were sacrificed and tumors were surgically removed for hematoxylin-eosin (H&E) staining.For the metastasis model, MTTL3 stable overexpressed SW620 cells (1 × 10⁶) or control cells were injected into the exposed spleen of the anesthetized BALB/C nude mice, respectively. After 21 days, liver metastases were carefully detected using a fluorescent stereoscope and embedded for H&E staining.
Response Summary	METTL3-catalyzed m6A modification in CRC tumorigenesis, wherein it facilitates CRC tumor growth and metastasis through suppressing Protein yippee-like 5 (YPEL5) expression in an m6A-YTHDF2-dependent manner.

Protocadherin Fat 4 (FAT4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HUVEC cell line	Homo sapiens
Treatment: shMETTL3 HUVEC cells Control: shScramble HUVEC cells		GSE157544
Regulation		logFC: 9.37E-01 p-value: 7.13E-05
More Results	Click to View More RNA-seq Results

Diseases of arteries or arterioles [ICD-11: BD5Y]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[96]
Responsed Disease	Diseases of arteries or arterioles [ICD-11: BD5Y]
Target Regulation	Down regulation
In-vitro Model	ACBRI-183 (Human retinal pericytes (ACBRI-183) was obtained from Cell Systems Corp. (CSC, USA))
In-vivo Model	Mettl3 floxed mice were purchased from GemPharmatech Co. Ltd (Nanjing, China). Pdgfr-Beta-Cre mice were purchased from Beijing Biocytogen Co. Ltd (Beijing, China) generated on C57BL/6J background. Mettl3 ^flox/flox mice were crossed with Pdgfr-Beta-Cre mice to generate pericyte-specific Mettl3 knockout mice. All mice were bred under the specific-pathogen free condition with free access to diet and water or their nursing mothers with alternating 12/12 light-dark cycle (lights on at 08:00 and off at 20:00).
Response Summary	Specific depletion of METTL3 in pericytes suppressed diabetes-induced pericyte dysfunction and Microvascular complication in vivo. METTL3 overexpression impaired pericyte function by repressing PKC-Eta, Protocadherin Fat 4 (FAT4), and PDGFRA expression, which was mediated by YTHDF2-dependent mRNA decay.

RAC-alpha serine/threonine-protein kinase (AKT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Liver	Mus musculus
Treatment: Mettl3 knockout liver Control: Wild type liver cells		GSE198512
Regulation		logFC: 1.27E+00 p-value: 1.77E-02
More Results	Click to View More RNA-seq Results

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[9]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Down regulation
Pathway Response	Apoptosis	hsa04210
Cell Process	Cell differentiation and apoptosis
In-vitro Model	HSPC (Human hematopoietic stem cell)
In-vivo Model	500,000 selected cells were injected via tail vein or retro-orbital route into female NSG (6-8 week old) recipient mice that had been sublethally irradiated with 475 cGy one day before transplantation.
Response Summary	METTL3 depletion in human myeloid leukemia cell lines induces cell differentiation and apoptosis and delays leukemia progression in recipient mice in vivo. Single-nucleotide-resolution mapping of m6A coupled with ribosome profiling reveals that m6A promotes the translation of c-MYC, BCL2 and PTEN mRNAs in the human acute myeloid leukemia MOLM-13 cell line. Moreover, loss of METTL3 leads to increased levels of phosphorylated RAC-alpha serine/threonine-protein kinase (AKT1).

Esophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[212]
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
	Wnt signaling pathway			hsa04310
	mTOR signaling pathway			hsa04150
	Apoptosis			hsa04210
Cell Process	Cell proliferation and invasion
	Cell apoptosis
In-vitro Model	Eca-109	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
	Normal esophageal epithelial cell line (HEEC) (Isolated from the human esophagus)
Response Summary	METTL3 plays a carcinogenic role in human EC progression partially through RAC-alpha serine/threonine-protein kinase (AKT1) signaling pathways, suggesting that METTL3 serves as a potential therapeutic target for esophageal cancer therapy. A double-effect inhibitor (BEZ235) inhibited AKT and mTOR phosphorylation and hindered the effect of METTL3 overexpression on the proliferation and migration of Eca-109 and KY-SE150 cells.

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
Response Summary	Down-regulation of METTL3 inhibits the proliferation and mobility of human gastric cancer cells and leads to inactivation of the AKT signaling pathway, suggesting that METTL3 is a potential target for the treatment of human gastric cancer. METTL3 knockdown decreased Bcl2 and increased Bax and active Caspase-3 in gastric cancer cells, which suggested the apoptotic pathway was activated. METTL3 led to inactivation of the AKT signaling pathway in human gastric cancer cells, including decreased phosphorylation levels of RAC-alpha serine/threonine-protein kinase (AKT1) and expression of down-stream effectors p70S6K and Cyclin D1.

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[213]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Up regulation
Response Summary	METTL3 contributes to the progression and chemoresistance of NSCLC by promoting RAC-alpha serine/threonine-protein kinase (AKT1) protein expression through regulating AKT1 mRNA m6A levels, and provides an efficient therapeutic intervention target for overcoming chemoresistance in NSCLC.

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[168]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell cycle
	Cell apoptosis
In-vitro Model	OVCAR-3	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
Response Summary	METTL3 knockdown downregulated the phosphorylation levels of RAC-alpha serine/threonine-protein kinase (AKT1) and the expression of the downstream effector Cyclin D1 in ovarian cancer.

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[62]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Up regulation
Pathway Response	Oxidative phosphorylation			hsa00190
In-vitro Model	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	RWPE-1	Normal	Homo sapiens	CVCL_3791
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
In-vivo Model	Approximately 2 × 10⁶ PCa cells (PC-3 shNC, shYTHDF2, shMETTL3 cell lines) per mouse suspended in 100 uL PBS were injected in the flank of male BALB/c nude mice (4 weeks old). During the 40-day observation, the tumor size (V = (width2×length ×0.52)) was measured with vernier caliper. Approximately 1.5 × 10⁶ PCa cells suspended in 100 uL of PBS (PC-3 shNC, shYTHDF2, and shMETTL3 cell lines) per mouse were injected into the tail vein of male BALB/c nude mice (4 weeks old). The IVIS Spectrum animal imaging system (PerkinElmer) was used to evaluate the tumor growth (40 days) and whole metastasis conditions (4 weeks and 6 weeks) with 100 uL XenoLight D-luciferin Potassium Salt (15 mg/ml, Perkin Elmer) per mouse. Mice were anesthetized and then sacrificed for tumors and metastases which were sent for further organ-localized imaging as above, IHC staining and hematoxylin-eosin (H&E) staining.
Response Summary	Knock-down of YTHDF2 or METTL3 significantly induced the expression of LHPP and NKX3-1 at both mRNA and protein level with inhibited phosphorylated RAC-alpha serine/threonine-protein kinase (AKT1). YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer.

Renal cell carcinoma [ICD-11: 2C90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[109]
Responsed Disease	Renal cell carcinoma [ICD-11: 2C90]
Target Regulation	Down regulation
Cell Process	Epithelial-to-mesenchymal transition
Cell Process	Arrest cell cycle at G0/G1 phase
In-vitro Model	ACHN	Papillary renal cell carcinoma	Homo sapiens	CVCL_1067
	Caki-1	Clear cell renal cell carcinoma	Homo sapiens	CVCL_0234
	Caki-2	Papillary renal cell carcinoma	Homo sapiens	CVCL_0235
	HK2	Normal	Acipenser baerii	CVCL_YE28
In-vivo Model	Cells (5×10⁶ cells in 200 uL) were suspended with 100 uL PBS and 100 uL Matrigel Matrix, and injected subcutaneously into the left armpit of each mouse.
Response Summary	Knockdown of METTL3 could obviously promote cell proliferation, migration and invasion function, and induce G0/G1 arrest,METTL3 acts as a novel marker for tumorigenesis, development and survival of RCC. Knockdown of METTL3 promoted changes in pI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR markers' expression with a gain in p-PI3k, p-AKT, p-mTOR and p-p70, and a loss of p-4EBP1.

Retina cancer [ICD-11: 2D02]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[44]
Responsed Disease	Retinoblastoma [ICD-11: 2D02.2]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
	mTOR signaling pathway			hsa04150
	Apoptosis			hsa04210
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	WERI-Rb-1	Retinoblastoma	Homo sapiens	CVCL_1792
	Y-79	Retinoblastoma	Homo sapiens	CVCL_1893
In-vivo Model	To establish a subcutaneous tumour model in nude mice, 2 × 10⁷ Y79 cells (METTL3 knockdown group: shNC, shRNA1 and shRNA2; METTL3 up-regulated group: NC and METLL3) were resuspended in 1 mL of pre-cooled PBS, and 200 uL of the cell suspension was injected subcutaneously into the left side of the armpit to investigate tumour growth (4 × 10⁶ per mouse).
Response Summary	METTL3 promotes the progression of retinoblastoma through PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR pathways in vitro and in vivo. METTL3 has an impact on the PI3K-AKT-mTOR-P70S6K/4EBP1 pathway. The cell proliferation results show that the stimulatory function of METTL3 is lost after rapamycin treatment.

Ragulator complex protein LAMTOR5 (LAMTOR5/HBXIP)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Th1 cell line	Mus musculus
Treatment: METTL3 knockout splenic Th1 cells Control: Wild type splenic Th1 cells		GSE129648
Regulation		logFC: -6.20E-01 p-value: 1.93E-04
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[214]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
Cell Process	Cell differentiation and apoptosis
	Glutamine metabolism
	Apoptosis (hsa04210)
Response Summary	Ragulator complex protein LAMTOR5 (LAMTOR5/HBXIP) up-regulates METTL3 by suppressing let-7g, in which METTL3 increased HBXIP expression forming a positive feedback loop of HBXIP/let-7g/METTL3/HBXIP, leading to accelerated cell proliferation in breast cancer.

Rho GTPase activating protein 5 (ARHGAP5)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Pancreatic islets	Mus musculus
Treatment: Mettl3 knockout mice Control: Mettl3 flox/flox mice		GSE155612
Regulation		logFC: 9.85E-01 p-value: 6.23E-05
More Results	Click to View More RNA-seq Results

Gastric cancer [ICD-11: 2B72]

In total 3 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[215]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular Processes
	Transport and catabolism
In-vitro Model	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
Response Summary	ARHGAP5-AS1 also stabilized ARHGAP5 mRNA in the cytoplasm by recruiting METTL3 to stimulate m6A modification of Rho GTPase activating protein 5 (ARHGAP5) mRNA. As a result, ARHGAP5 was upregulated to promote chemoresistance and its upregulation was also associated with poor prognosis in gastric cancer. downregulation of ARHGAP5-AS1 in resistant cells evidently reversed the resistance to chemotherapeutic drugs including cisplatin (DDP), ADM, and 5-FU.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[215]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Responsed Drug	Fluorouracil		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular processes
	Cellular transport, Cellular catabolism
In-vitro Model	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
Response Summary	ARHGAP5-AS1 also stabilized ARHGAP5 mRNA in the cytoplasm by recruiting METTL3 to stimulate m6A modification of Rho GTPase activating protein 5 (ARHGAP5) mRNA. As a result, ARHGAP5 was upregulated to promote chemoresistance and its upregulation was also associated with poor prognosis in gastric cancer. downregulation of ARHGAP5-AS1 in resistant cells evidently reversed the resistance to chemotherapeutic drugs including cisplatin (DDP), ADM, and 5-FU.
Experiment 3 Reporting the m6A-centered Disease Response of This Target Gene				[215]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Responsed Drug	Adriamycin		Phase 3	Drug Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular processes
	Cellular transport, Cellular catabolism
In-vitro Model	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
Response Summary	ARHGAP5-AS1 also stabilized ARHGAP5 mRNA in the cytoplasm by recruiting METTL3 to stimulate m6A modification of Rho GTPase activating protein 5 (ARHGAP5) mRNA. As a result, ARHGAP5 was upregulated to promote chemoresistance and its upregulation was also associated with poor prognosis in gastric cancer. downregulation of ARHGAP5-AS1 in resistant cells evidently reversed the resistance to chemotherapeutic drugs including cisplatin (DDP), ADM, and 5-FU.

Serine-protein kinase ATM (ATM)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	ARPE-19 cell line	Homo sapiens
Treatment: shMETTL3 ARPE-19 cells Control: shControl ARPE-19 cells		GSE202017
Regulation		logFC: -7.38E-01 p-value: 7.12E-06
More Results	Click to View More RNA-seq Results

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[216]
Responsed Disease	Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Target Regulation	Down regulation
Pathway Response	Homologous recombination			hsa03440
	p53 signaling pathway			hsa04115
In-vitro Model	BJAB	Burkitt lymphoma	Homo sapiens	CVCL_5711
	Raji	EBV-related Burkitt lymphoma	Homo sapiens	CVCL_0511
Response Summary	m6A modification regulates ATM mRNA metabolism and ATM downstream signaling, which illustrates the importance of m6A modification-related molecules for being used as therapeutic targets in DNA damage-related diseases. METTL3 disrupts the ATM stability via m6A modification, thereby affecting the DNA-damage response.

Serine/arginine-rich splicing factor 11 (SRSF11)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Liver	Mus musculus
Treatment: Mettl3 knockout liver Control: Wild type liver cells		GSE198512
Regulation		logFC: -6.30E-01 p-value: 2.77E-03
More Results	Click to View More RNA-seq Results

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[217]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Target Regulation	Up regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	mRNA decay
In-vitro Model	U251 (Fibroblasts or fibroblast like cells)
	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
In-vivo Model	For subcutaneous tumor model, each mouse was injected subcutaneously in the right flank with 2 × 10⁶ U87MG cells (METTL3-KD or control) in 100 uL PBS.
Response Summary	Silencing METTL3 or overexpressing dominant-negative mutant METTL3 suppressed the growth and self-renewal of Glioblastoma cells. Integrated transcriptome and MeRIP-seq analyses revealed that downregulating the expression of METTL3 decreased m6A modification levels of Serine/arginine-rich splicing factor 11 (SRSF11), which led to YTHDC1-dependent NMD of SRSF transcripts and decreased SRSF protein expression.

Serine/arginine-rich splicing factor 3 (SRSF3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LNCaP cell line	Homo sapiens
Treatment: shMETTL3 LNCaP cells Control: shControl LNCaP cells		GSE147884
Regulation		logFC: -6.96E-01 p-value: 4.00E-41
More Results	Click to View More RNA-seq Results

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[217]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Target Regulation	Up regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	mRNA decay
In-vitro Model	U251 (Fibroblasts or fibroblast like cells)
	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
In-vivo Model	For subcutaneous tumor model, each mouse was injected subcutaneously in the right flank with 2 × 10⁶ U87MG cells (METTL3-KD or control) in 100 uL PBS.
Response Summary	Silencing METTL3 or overexpressing dominant-negative mutant METTL3 suppressed the growth and self-renewal of Glioblastoma cells. Integrated transcriptome and MeRIP-seq analyses revealed that downregulating the expression of METTL3 decreased m6A modification levels of Serine/arginine-rich splicing factor 3 (SRSF3), which led to YTHDC1-dependent NMD of SRSF transcripts and decreased SRSF protein expression.

Serine/arginine-rich splicing factor 6 (SRSF6)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HeLa cell line	Homo sapiens
Treatment: METTL3 knockdown HeLa cells Control: HeLa cells		GSE70061
Regulation		logFC: 2.87E+00 p-value: 5.80E-03
More Results	Click to View More RNA-seq Results

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[217]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Target Regulation	Up regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	mRNA decay
In-vitro Model	U251 (Fibroblasts or fibroblast like cells)
	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
In-vivo Model	For subcutaneous tumor model, each mouse was injected subcutaneously in the right flank with 2 × 10⁶ U87MG cells (METTL3-KD or control) in 100 uL PBS.
Response Summary	Silencing METTL3 or overexpressing dominant-negative mutant METTL3 suppressed the growth and self-renewal of Glioblastoma cells. Integrated transcriptome and MeRIP-seq analyses revealed that downregulating the expression of METTL3 decreased m6A modification levels of Serine/arginine-rich splicing factor 6 (SRSF6), which led to YTHDC1-dependent NMD of SRSF transcripts and decreased SRSF protein expression.

Serine/threonine-protein kinase PLK1 (PLK1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -8.98E-01 p-value: 1.15E-18
More Results	Click to View More RNA-seq Results

Pulpitis [ICD-11: DA09]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[218]
Responsed Disease	Pulpitis [ICD-11: DA09]
Target Regulation	Down regulation
Cell Process	Cell senescence
In-vitro Model	DPSC	Normal	Homo sapiens	CVCL_AV90
Response Summary	Impaired METTL3 expression in dental pulp stem cells led to increasing cell senescence and apoptosis by interfering with the mitotic cell cycle in a m6A-dependent manner. The protein interaction network of differentially expressed genes identified Serine/threonine-protein kinase PLK1 (PLK1), a critical cycle modulator, as the target of METTL3-mediated m6A methylation in DPSCs.

Signal transducer and activator of transcription 3 (STAT3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Embryonic stem cells	Mus musculus
Treatment: METTL3 knockout mESCs Control: Wild type mESCs		GSE156481
Regulation		logFC: -6.99E-01 p-value: 1.19E-15
More Results	Click to View More RNA-seq Results

Atherosclerosis [ICD-11: BD40]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[130]
Responsed Disease	Atherosclerosis [ICD-11: BD40.Z]
Target Regulation	Up regulation
Pathway Response	JAK-STAT signaling pathway			hsa04630
Cell Process	Cell proliferation and migration
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
In-vivo Model	The adeno-associated viruses (AAV) that could silence METTL3 (sh-METTL3) and the negative control adeno-associated viruses (sh-NC) were obtained from WZ Biosciences Inc. (Jinan, China). APOE^-/- mice were randomly divided into AS + sh-NC and AS + sh-METTL3 groups. Each group contains five mice. Mice were fed with the standard diet for 1 week to acclimatize. After 1 week of acclimation, mice were challenged with a high-fat and high-cholesterol feed H10540 (Beijing HFK BIOSCIENCE Co., Ltd., Beijing, China). The formula of the H10540 feed was shown in Supplementary File S1. After 8 weeks of HFD feeding, sh-NC or sh-METTL3 adeno-associated virus serotype 9 (AAV9, 1012 viral genome copies per mouse) were respectively delivered into mice in AS + sh-NC or AS + sh-METTL3 group through tail vein injection. At 14 weeks after HDF feeding, mice fasted overnight.
Response Summary	METTL3 knockdown prevented Atherosclerosis progression by inhibiting JAK2/Signal transducer and activator of transcription 3 (STAT3) pathway via IGF2BP1.

Spectrin beta, non-erythrocytic 2 (SPTBN2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -1.19E+00 p-value: 2.92E-45
More Results	Click to View More RNA-seq Results

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[219]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Cell Process	Cell proliferation and metastasis
	Cell apoptosis
In-vitro Model	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
In-vivo Model	The growth of CC cells in vivo was examined by subcutaneous injection of LoVo cells or Caco-2 cells into NSG mice, while the metastatic ability of cells in vivo by intracardiac injection into mice.
Response Summary	Overexpression of LINC01605, regulated by SMYD2-EP300-mediated H3K27ac and H3K4me3 modifications, bound to METTL3 protein to promote m6A modification of Spectrin beta, non-erythrocytic 2 (SPTBN2) mRNA, leading to the development of colorectal cancer.

Sprouty-related, EVH1 domain-containing protein 2 (SPRED2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Embryonic stem cells	Mus musculus
Treatment: METTL3 knockout mESCs Control: Wild type mESCs		GSE156481
Regulation		logFC: 5.88E-01 p-value: 1.67E-05
More Results	Click to View More RNA-seq Results

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[220]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	Cell migration and invasion
In-vitro Model	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	NCM460	Normal	Homo sapiens	CVCL_0460
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
In-vivo Model	The spleen in the upper left lateral abdomen of the anesthetized mice were exposed, 10⁶ cells suspended in 20 uL phosphate-buffered saline (PBS) were injected into the distal tip of the spleen. After injection, replacing the spleen, and closing the incision.
Response Summary	METTL3/miR-1246/Sprouty-related, EVH1 domain-containing protein 2 (SPRED2) axis plays an important role in tumor metastasis and provides a new m6A modification pattern in Colorectal cancer development.

Stromelysin-1 (MMP-3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HUVEC cell line	Homo sapiens
Treatment: shMETTL3 HUVEC cells Control: shScramble HUVEC cells		GSE157544
Regulation		logFC: -1.52E+00 p-value: 7.27E-05
More Results	Click to View More RNA-seq Results

Rheumatoid arthritis [ICD-11: FA20]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[187]
Responsed Disease	Rheumatoid arthritis [ICD-11: FA20]
Target Regulation	Up regulation
Cell Process	Inflammatory response
In-vitro Model	FLS (Rat fibroblast synovial cell line)
In-vivo Model	To establish the adjuvant-induced arthritis (AIA) model, the rats were given complete Freund's adjuvant (CFA; Chondrex, Inc.) on the left paw of 0.1 ml per 100 g of body weight. Additionally, the rats were injected with normal saline to create the negative control (NC) group.
Response Summary	METTL3 knockdown suppressed interleukin (IL)-6, matrix metalloproteinase Stromelysin-1 (MMP-3), and MMP-9 levels in human RA-FLSs and rat AIA-FLSs.

Suppressor of cytokine signaling 2 (SOCS2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	ARPE-19 cell line	Homo sapiens
Treatment: shMETTL3 ARPE-19 cells Control: shControl ARPE-19 cells		GSE202017
Regulation		logFC: 8.91E-01 p-value: 2.94E-04
More Results	Click to View More RNA-seq Results

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[221]
Responsed Disease	Glioma [ICD-11: 2A00.0]
Target Regulation	Down regulation
Pathway Response	Transcriptional misregulation in cancer			hsa05202
Cell Process	RNA stability
In-vitro Model	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	LN-18	Glioblastoma	Homo sapiens	CVCL_0392
	HEB (human normal glial cell line HEB were obtained from Tongpai (Shanghai) biotechnology co., LTD (Shanghai, China))
In-vivo Model	Mice were subcutaneously injected with 2.5 × 10⁶ U251 cells stably infected with OE-NC, OE-JMJD1C, OE-NC and sh-NC, OE-JMJD1C and sh-NC or OE-JMJD1C and sh-SOCS2 (n = 10 in each group) in 0.1 ml PBS.
Response Summary	miR-302a was identified to target METTL3, which could inhibit Suppressor of cytokine signaling 2 (SOCS2) expression via m6A modification in glioma.

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[222]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
Response Summary	METTL3-KO in gastric cancer cells resulted in the suppression of cell proliferation by inducing Suppressor of cytokine signaling 2 (SOCS2), suggesting a potential role of elevated METTL3 expression in gastric cancer progression.

Colon cancer [ICD-11: 2B90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[223]
Responsed Disease	Colon cancer [ICD-11: 2B90]
Target Regulation	Down regulation
Cell Process	Cell proliferation
In-vitro Model	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	An increased level of METTL3 may maintain the tumorigenicity of colon cancer cells by suppressing Suppressor of cytokine signaling 2 (SOCS2).

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[224]
Responsed Disease	Liver cancer [ICD-11: 2C12]
Target Regulation	Down regulation
Cell Process	Cells proliferation
	Cells migration
	Cells invasion
	RNA degradation (hsa03018)
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	MHCC97-L	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4973
In-vivo Model	For the subcutaneous implantation model, 2 × 10⁶ METTL3 stable knockdown Huh-7 cells or METTL3 overexpression MHCC97L cells were injected subcutaneously into BABL/cAnN-nude mice. For orthotopic implantation, wild-type and METTL3 knockout Huh-7 cells were luciferase labelled, and 2 × 10⁶ cells were then injected orthotopically into the left liver lobe of nude mice.
Response Summary	METTL3 is frequently up-regulated in human HCC and contributes to HCC progression. METTL3 represses Suppressor of cytokine signaling 2 (SOCS2) expression in HCC through an m6A-YTHDF2-dependent mechanism.

Thyrotoxicosis [ICD-11: 5A02]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[225]
Responsed Disease	Graves disease [ICD-11: 5A02.0]
Target Regulation	Down regulation
In-vitro Model	PBMCs (Human peripheral blood mononuclear cells (PBMCs) are isolated from peripheral blood and identified as any blood cell with a round nucleus)
Response Summary	METTL3 knock-down experiment revealed that expressions of SOCS family members SOCS1, Suppressor of cytokine signaling 2 (SOCS2), SOCS4, SOCS5, and SOCS6 were increased after METTL3 knock-down. It indicated that METTL3 is involved in the development of Graves' disease (GD) by inducing mRNA m6A methylation modification of SOCS family members.

Thioredoxin (TXN/SASP)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HeLa cell line	Homo sapiens
Treatment: METTL3 knockdown HeLa cells Control: HeLa cells		GSE70061
Regulation		logFC: -7.32E-01 p-value: 1.61E-02
More Results	Click to View More RNA-seq Results

Osteoarthritis [ICD-11: FA05]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[131]
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular senescence
	Cell autophagy
In-vitro Model	C-28/I2	Normal	Homo sapiens	CVCL_0187
	FLS (Rat fibroblast synovial cell line)
In-vivo Model	Mice were anaesthetized with isoflurane supplied in a mouse anaesthesia apparatus, followed with joint surgery on the right joint by sectioning the medial meniscotibial ligament.
Response Summary	In osteoarthritis METTL3-mediated m6A modification decreased the expression of Thioredoxin (TXN/SASP), an E-1 enzyme crucial for the formation of autophagosomes, by attenuating its RNA stability. Silencing METTL3 enhanced autophagic flux and inhibited SASP expression in OA-FLS.

Thioredoxin domain-containing protein 5 (TXNDC5)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -6.19E-01 p-value: 4.11E-14
More Results	Click to View More RNA-seq Results

Melanoma [ICD-11: 2C30]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[226]
Responsed Disease	Melanoma [ICD-11: 2C30]
Target Regulation	Up regulation
Cell Process	Cell proliferation, cell migration,cell invasion
In-vitro Model	SK-MEL-28	Cutaneous melanoma	Homo sapiens	CVCL_0526
	MV3	Amelanotic melanoma	Homo sapiens	CVCL_W280
	HMY-1	Melanoma	Homo sapiens	CVCL_2950
	HEMa (The normal human epidermal melanocyte (HEMa) was extracted from fresh foreskin tissue donated after circumcision in adults and cultured in melanocyte medium with 5% fetal bovine serum (Sciencell, USA))
	A-875	Melanoma	Homo sapiens	CVCL_4733
	A375-MA2	Amelanotic melanoma	Homo sapiens	CVCL_X495
	A2058	Amelanotic melanoma	Homo sapiens	CVCL_1059
In-vivo Model	Sixteen BALB/c nude mice (male, 6-week-old) were raised under pathogen-free conditions and randomly divided into two groups. A total of 2 × 10⁶ A375 NTC or sh-METTL3#2 cells were subcutaneously inoculated into the right hind flank. Body weight and tumor size were measured every other day. The tumors were harvested at the end of the observation period, and tumor weight and gross images were recorded (11 days after inoculation). The tumors were embedded in RNA later and 10% formalin for further detection.
Response Summary	METTL3 regulates certain m6A-methylated transcripts, Thioredoxin domain-containing protein 5 (TXNDC5), targeting the m6A dependent-METTL3 signaling pathway serves as a promising therapeutic strategy for management of patients of acral melanomas.

Transcription factor AP-2-alpha (TFAP2A)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 9.80E-01 p-value: 2.54E-26
More Results	Click to View More RNA-seq Results

Urinary/pelvic organs injury [ICD-11: NB92]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[38]
Responsed Disease	Injury of kidney [ICD-11: NB92.0]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	NRK-52E	Normal	Rattus norvegicus	CVCL_0468
In-vivo Model	Rats were anesthetized and incised through the midline of the abdomen, and the left renal vertebral arch and arteries were blocked for 45 min, thereby resulting in left kidney ischemia. At the same time, the right kidney was removed, further aggravating the degree of left kidney injury.
Response Summary	METTL3 contributes to renal ischemia-reperfusion injury by regulating Foxd1 methylation. When METTL3 was inhibited, m6A levels were accordingly decreased and cell apoptosis was suppressed in the H/R in vitro model. Based on MeRIP sequencing, Transcription factor AP-2-alpha (TFAP2A), cytochrome P-450 1B1 (cyp1b1), and forkhead box D1 (foxd1) were significantly differentially expressed, as was m6A, which is involved in the negative regulation of cell proliferation and kidney development.

Transcription factor p65 (RELA)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: 6.33E-01 p-value: 3.93E-11
More Results	Click to View More RNA-seq Results

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[4]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Up regulation
Cell Process	Glucose metabolism
Response Summary	AF4/FMR2 family member 4 (AFF4), two key regulators of NF-Kappa-B pathway (IKBKB and Transcription factor p65 (RELA)) and MYC were further identified as direct targets of METTL3-mediated m6A modification.overexpression of METTL3 significantly promoted Bladder cancer cell growth and invasion.

Thyroid Cancer [ICD-11: 2D10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[103]
Responsed Disease	Papillary thyroid cancer [ICD-11: 2D10.1]
Target Regulation	Down regulation
Pathway Response	NF-kappa B signaling pathway			hsa04064
In-vitro Model	TPC-1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
	Nthy-ori 3-1	Normal	Homo sapiens	CVCL_2659
	KTC-1	Thyroid carcinoma	Homo sapiens	CVCL_6300
	B-CPAP	Thyroid gland carcinoma	Homo sapiens	CVCL_0153
In-vivo Model	For xenograft models, 5 × 10⁶ BCPAP or KTC-1 cells from each group were injected subcutaneously into the flanks of female BALB/c nude mice (4-6 weeks old, Shanghai SLAC Laboratory Animal, China, n = 5 per group) in a volume of 150 uL PBS. Tumor growth was measured with a digital caliper every 4 days and calculated using the following formula: (length × width2)/2. To study the effect of IL-8 on tumor growth in vivo, scramble or shMETTL3 BCPAP cells were implanted hypodermically into BALB/c nude mice (2 × 10⁶ cells in 150 uL PBS, n = 10 per group). When palpable tumors formed on day 14, mice were treated with DMSO or the IL-8 inhibitor SB225002 (10 mg/kg) by intraperitoneal injection 3 times per week for 3 weeks. Six weeks post-injection, the mice were sacrificed, and the tumors were collected to analyze the frequency of TANs by flow cytometry. For the lung metastasis model, BCPAP and KTC-1 cells (2 × 10⁶ cells in 100 uL PBS) with the corresponding vectors were injected into the tail veins of BALB/c nude mice. Eight weeks after injection, the mice were euthanized, and metastatic lung nodules were analyzed (n = 5 for each group).
Response Summary	METTL3 played a pivotal tumor-suppressor role in papillary thyroid cancer carcinogenesis through c-Rel and Transcription factor p65 (RELA) inactivation of the nuclear factor Kappa-B (NF-Kappa-B) pathway by cooperating with YTHDF2 and altered TAN infiltration to regulate tumor growth.

Transcription factor Sp1 (SP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Mouse testis	Mus musculus
Treatment: Mettl3 knockout mouse testis Control: Mouse testis		GSE99771
Regulation		logFC: -5.88E+00 p-value: 2.22E-06
More Results	Click to View More RNA-seq Results

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[227]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Cell Process	Cell cycle
In-vitro Model	EoL-1	Chronic eosinophilic leukemia	Homo sapiens	CVCL_0258
	HEL	Erythroleukemia	Homo sapiens	CVCL_0001
	HL-60	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	Jurkat	T acute lymphoblastic leukemia	Homo sapiens	CVCL_0065
	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	KG-1	Adult acute myeloid leukemia	Homo sapiens	CVCL_0374
	Loucy	Adult T acute lymphoblastic leukemia	Homo sapiens	CVCL_1380
	MOLM-13	Adult acute myeloid leukemia	Homo sapiens	CVCL_2119
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	NOMO-1	Adult acute monocytic leukemia	Homo sapiens	CVCL_1609
	RN2c (Acute myeloid leukemia cell line)
	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
In-vivo Model	Performed an ex vivo genome wide CRISPR dropout screen (Screen 1) using Cas9-expressing mouse primary leukaemia cells driven by an MLL-AF9 fusion gene and a FLT3 internal tandem duplication.
Response Summary	Genes regulated by METTL3 in this way are necessary for acute myeloid leukaemia. Two genes expressing the transcription factors Transcription factor Sp1 (SP1) and SP2, which have promoters occupied by METTL3.

Transcription factor Sp2 (SP2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Pancreatic islets	Mus musculus
Treatment: Mettl3 knockout mice Control: Mettl3 flox/flox mice		GSE155612
Regulation		logFC: 8.11E-01 p-value: 3.84E-03
More Results	Click to View More RNA-seq Results

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[227]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Cell Process	Cell cycle
In-vitro Model	EoL-1	Chronic eosinophilic leukemia	Homo sapiens	CVCL_0258
	HEL	Erythroleukemia	Homo sapiens	CVCL_0001
	HL-60	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	Jurkat	T acute lymphoblastic leukemia	Homo sapiens	CVCL_0065
	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	KG-1	Adult acute myeloid leukemia	Homo sapiens	CVCL_0374
	Loucy	Adult T acute lymphoblastic leukemia	Homo sapiens	CVCL_1380
	MOLM-13	Adult acute myeloid leukemia	Homo sapiens	CVCL_2119
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
	NOMO-1	Adult acute monocytic leukemia	Homo sapiens	CVCL_1609
	RN2c (Acute myeloid leukemia cell line)
	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
In-vivo Model	Performed an ex vivo genome wide CRISPR dropout screen (Screen 1) using Cas9-expressing mouse primary leukaemia cells driven by an MLL-AF9 fusion gene and a FLT3 internal tandem duplication.
Response Summary	Genes regulated by METTL3 in this way are necessary for acute myeloid leukaemia. Two genes expressing the transcription factors SP1 and Transcription factor Sp2 (SP2), which have promoters occupied by METTL3.

Transcriptional repressor protein YY1 (YY1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Pancreatic islets	Mus musculus
Treatment: Mettl3 knockout mice Control: Mettl3 flox/flox mice		GSE155612
Regulation		logFC: 9.11E-01 p-value: 3.29E-04
More Results	Click to View More RNA-seq Results

Multiple myeloma [ICD-11: 2A83]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[228]
Responsed Disease	Multiple myeloma [ICD-11: 2A83.1]
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	U266 (Human multiple myeloma cells)
	RPMI-8226	Plasma cell myeloma	Homo sapiens	CVCL_0014
	NCI-H929	Plasma cell myeloma	Homo sapiens	CVCL_1600
	MM1.S	Plasma cell myeloma	Homo sapiens	CVCL_8792
In-vivo Model	BALB/C nude mice (5 weeks old, weighing 18-22 g) were fed in specific pathogen-free facilities and subcutaneously inoculated with U266 cells (1 × 10⁶). The mice were randomly divided into 3 groups with 6 mice per group, when the tumor was measurable. Then, miR-27a-3p mimic or sh-METTL3 was injected intratumorally at an interval of 4 days a total of 4 times. Tumor volume was measured using a digital caliper every week and calculated using the formula V = 1/2 (width2 × length).
Response Summary	METTL3 affected the growth, apoptosis, and stemness of MM cells through accelerating the stability of Transcriptional repressor protein YY1 (YY1) mRNA and the maturation of primary-miR-27a-3p in vitro and in vivo.

Tyrosine-protein kinase receptor UFO (AXL)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -1.33E+00 p-value: 3.11E-06
More Results	Click to View More RNA-seq Results

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[229]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	A2780	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	COV504	Ovarian carcinoma	Homo sapiens	CVCL_2424
	ES2	Ewing sarcoma	Homo sapiens	CVCL_AX39
	HO-8910	Endocervical adenocarcinoma	Homo sapiens	CVCL_6868
	OVCAR-3	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vivo Model	2 × 10⁶ tumor cells (OVCAR3-METTL3 and OVCAR3-Ctrl) or 1 × 10⁶ tumor cells (SKOV3-shMETTL3-1, SKOV3-shMETTL3-2 and SKOV3-shNC) were suspended in 200 uL of RPMI 1640 complete culture medium with 25% Matrigel (BD Biosciences) and inoculated subcutaneously into the right flank of the nude mice.
Response Summary	METTL3 promoted epithelial-mesenchymal transition (EMT) by upregulating the receptor tyrosine kinase Tyrosine-protein kinase receptor UFO (AXL) and that METTL3 serves as a novel prognostic and/or therapeutic target of interest in ovarian cancer.

Ubiquitin carboxyl-terminal hydrolase 4 (USP4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Mouse testis	Mus musculus
Treatment: Mettl3 knockout mouse testis Control: Mouse testis		GSE99771
Regulation		logFC: -6.58E+00 p-value: 2.47E-06
More Results	Click to View More RNA-seq Results

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[163]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Down regulation
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
In-vivo Model	A total of 1 × 10⁶ PC3 cells or DU145 cells suspended in a mixture of 100 uL PBS and Matrigel were subcutaneously injected into BALB/c nude mice. Tumor weight were measured 2 months after the engraftment. To evaluate the role of METTL3 in tumor metastasis, PC3 cells with or without knockdown of METTL3 were injected into SCID mice through the tail vein (1 × 10⁶ cells per mouse). After eight weeks, mice were sacrificed and their lung tissues were collected for subsequent analyses.
Response Summary	m6A modification levels were markedly upregulated in human PCa tissues due to increased expression of METTL3. METTL3 mediates m6A modification of Ubiquitin carboxyl-terminal hydrolase 4 (USP4) mRNA at A2696, and m6A reader protein YTHDF2 binds to and induces degradation of USP4 mRNA by recruiting RNA-binding protein HNRNPD to the mRNA. Decrease of USP4 fails to remove the ubiquitin group from ELAVL1 protein, resulting in a reduction of ELAVL1 protein. Lastly, downregulation of ELAVL1 in turn increases ARHGDIA expression, promoting migration and invasion of PCa cells.

Ubiquitin carboxyl-terminal hydrolase 7 (USP7)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Liver	Mus musculus
Treatment: Mettl3 knockout liver Control: Wild type liver cells		GSE198513
Regulation		logFC: -7.46E-01 p-value: 2.02E-26
More Results	Click to View More RNA-seq Results

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[230]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Cell Process	Cell invasion
	Cell migration
	Cell proliferation
In-vitro Model	MHCC97-L	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4973
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
In-vivo Model	Male nu/nu mice between 4 and 6 weeks of age received subcutaneous injections of equivalent Hep3B cells expressing either LV-shMETTL3 or LV-USP7 within 30 min of harvesting on the right and left flanks. The tumor was weighed after approximately 4 weeks, and the volume was measured every 5 days.
Response Summary	METTL3 regulates the expression of Ubiquitin carboxyl-terminal hydrolase 7 (USP7) through m6A methylation and facilitate the invasion, migration and proliferation of HCC cells. Besides, the elevated METTL3 expression was related to worse overall survival.

Ubiquitin-like-conjugating enzyme ATG3 (ATG3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Liver	Mus musculus
Treatment: Mettl3-deficient liver Control: Wild type liver cells		GSE197800
Regulation		logFC: -1.62E+00 p-value: 2.55E-18
More Results	Click to View More RNA-seq Results

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[17]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib	Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including Ubiquitin-like-conjugating enzyme ATG3 (ATG3), ATG5, ATG7, ATG12, and ATG16L1.

UBX domain-containing protein 1 (UBXN1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Embryonic stem cells	Mus musculus
Treatment: METTL3 knockout mESCs Control: Wild type mESCs		GSE156481
Regulation		logFC: -9.05E-01 p-value: 4.00E-16
More Results	Click to View More RNA-seq Results

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[202]
Responsed Disease	Glioma [ICD-11: 2A00.0]
Target Regulation	Down regulation
Pathway Response	NF-kappa B signaling pathway			hsa04064
In-vitro Model	U87 (A primary glioblastoma cell line)
	N33 (The GBM patient-derived cell line)
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	H4	Astrocytoma	Homo sapiens	CVCL_1239
In-vivo Model	Five-week-old female BALB/c nude mice (Charles Rivers, Beijing, China) were selected for the experiments. U87 cells (5 × 10⁵) transfected with an empty vector, YTHDF2 overexpression, or METTL3 overexpression vectors were suspended in PBS and injected into the right frontal node of nude mice. The inoculation position was 2 mm lateral and 2 mm posterior to the anterior fontanel. Tumor size was estimated from luciferase volume measurements and MRI. The mice were sacrificed when they exhibited disturbed activity or convulsion. The brain was then harvested and embedded in paraffin.
Response Summary	YTHDF2 accelerated UBX domain-containing protein 1 (UBXN1) mRNA degradation via METTL3-mediated m6A, which, in turn, promoted NF-Kappa-B activation. YTHDF2 promotes the malignant progression of gliomas and revealed important insight into the upstream regulatory mechanism of NF-Kappa-B activation via UBXN1 with a primary focus on m6A modification.

Uridine-cytidine kinase 2 (UCK2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	ARPE-19 cell line	Homo sapiens
Treatment: shMETTL3 ARPE-19 cells Control: shControl ARPE-19 cells		GSE202017
Regulation		logFC: -6.22E-01 p-value: 2.07E-05
More Results	Click to View More RNA-seq Results

Melanoma [ICD-11: 2C30]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[232]
Responsed Disease	Melanoma [ICD-11: 2C30]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
In-vitro Model	Hs 294T	Melanoma	Homo sapiens	CVCL_0331
Response Summary	m6A-METTL3 axis induced abnormal Uridine-cytidine kinase 2 (UCK2) expression plays a role in melanoma metastasis by enhancing the Wnt/Bete-catenin pathway, which provided new clues for melanoma metastasis. It also provides a potential target for the prevention and treatment of melanoma.

Urokinase-type plasminogen activator (PLAU)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 1.68E+00 p-value: 4.01E-99
More Results	Click to View More RNA-seq Results

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[233]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	MAPK signaling pathway			hsa04010
In-vitro Model	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
In-vitro Model	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
In-vivo Model	1 × 10⁶ cells in 100 uL PBS (shMETTL3-1 or shNC) were respectively injected into each mouse through the tail vein. Pulmonary metastases were monitored after fourteen days using the imaging system (IVIS) Spectrum (PerkinElmer, USA).
Response Summary	METTL3 upregulated Urokinase-type plasminogen activator (PLAU) mRNA in an m6A-dependent manner, and then participated in MAPK/ERK pathway to promote angiogenesis and metastasis in CRC.

Vascular endothelial growth factor A (VEGFA)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shMETTL3 MOLM13 cells Control: MOLM13 cells		GSE98623
Regulation		logFC: -8.11E-01 p-value: 1.38E-19
More Results	Click to View More RNA-seq Results

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[46]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	NCM460	Normal	Homo sapiens	CVCL_0460
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
In-vivo Model	A total of 8 × 10⁶ wild-type (WT) or METTL3-knockdown cells were injected into the dorsal flanks of 6-week-old nude mice. Seven mice were randomly selected to calculate the volume according to the following formula: V = (width2 × length)/2. Mice were euthanized three weeks after injection and tumors removed, weighed, fixed, and embedded for immunohistochemical analysis.
Response Summary	EphA2 and Vascular endothelial growth factor A (VEGFA) targeted by METTL3 via different IGF2BP-dependent mechanisms were found to promote vasculogenic mimicry (VM) formation via PI3K/AKT/mTOR and ERK1/2 signaling in CRC.

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[6]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Up regulation
Cell Process	Cellular proliferation and survival
In-vitro Model	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
In-vitro Model	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
In-vivo Model	For induction of BCa, 6-8-week-old mice were treated with drinking water containing 500 ug/ml BBN for 16 weeks and then given normal water for another 10 weeks. Tamoxifen was intraperitonelly injected to the mice with 0.08 mg/g of body weight each day for 3 days in order to inductively knock out the target gene.
Response Summary	Deletion of Mettl3 leads to the suppression of TEK and Vascular endothelial growth factor A (VEGFA),ablation of Mettl3 in bladder urothelial attenuates the oncogenesis and tumor angiogenesis of bladder cancer.

Diseases of the musculoskeletal system [ICD-11: FC0Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[234]
Responsed Disease	Diseases of the musculoskeletal system [ICD-11: FC0Z]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway	hsa04151
Cell Process	Alternative splicing
In-vitro Model	BMSCs (BMSCs were obtained from the femurs and tibias of 2-3-week-old Sprague-Dawley male rats (Animal Center of Sun Yat-sen University))
Response Summary	Mettl3 knockdown not only reduced the expression of Vascular endothelial growth factor A (VEGFA) but also decreased the level of its splice variants, vegfa-164 and vegfa-188, in Mettl3-deficient BMSCs. These findings contribute to novel progress in understanding the role of epitranscriptomic regulation in the osteogenic differentiation of BMSCs.

Vimentin (vimentin)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -9.97E-01 p-value: 8.40E-43
More Results	Click to View More RNA-seq Results

Nasopharyngeal carcinoma [ICD-11: 2B6B]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[24]
Responsed Disease	Nasopharyngeal carcinoma [ICD-11: 2B6B]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	Neural progenitor cells (NPCs) (The progenitor cells of the CNS)
	NP69 (A human immortalized nasopharyngeal epithelial)
	HNE-2	Nasopharyngeal carcinoma	Homo sapiens	CVCL_FA07
	HNE-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_0308
	CNE-2	Nasopharyngeal carcinoma	Homo sapiens	CVCL_6889
	CNE-1	Normal	Homo sapiens	CVCL_6888
In-vivo Model	1 × 10⁵ HNE2 cells (with or without METTL3 knockdown) were labeled with luciferase gene and injected into the tail vein of the nude mice.
Response Summary	METTL3 activated the luciferase activity of TOPflash (a reporter for beta-catenin/TCF signaling), and downregulation of METTL3 inhibited the expression of beta-catenin/TCF target genes Vimentin (vimentin) and N-cadherin, which are two regulators of epithelial-mesenchymal transition. METTL3 silencing decreased the m6A methylation and total mRNA levels of Tankyrase, a negative regulator of axin. METTL3 is a therapeutic target for NPC.

Zinc finger protein SNAI1 (SNAI1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -7.78E-01 p-value: 5.01E-07
More Results	Click to View More RNA-seq Results

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[235]
Responsed Disease	Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Target Regulation	Up regulation
Pathway Response	Adherens junction			hsa04520
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
Response Summary	The expression of TGFbeta1 was up-regulated, while self-stimulated expression of TGFbeta1 was suppressed in METTL3Mut/- cells. m6A performed multi-functional roles in TGFbeta1 expression and EMT modulation, suggesting the critical roles of m6A in cancer progression regulation. Zinc finger protein SNAI1 (SNAI1), which was down-regulated in Mettl3Mut/- cells, was a key factor responding to TGF-Beta-1-induced EMT.

Nasopharyngeal carcinoma [ICD-11: 2B6B]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[236]
Responsed Disease	Nasopharyngeal carcinoma [ICD-11: 2B6B]
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	SUNE1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_6946
Response Summary	Overexpression of Zinc finger protein SNAI1 (SNAI1) partially reversed the regulatory effects of METTL3 on EMT-related gene expressions and metastatic abilities in nasopharyngeal carcinoma. Knockdown of METTL3 decreased the enrichment abundance of Snail in anti-IGF2BP2.

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[237]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	Adherens junction			hsa04520
Cell Process	Cell proliferation
Cell Process	Cell invasion
In-vitro Model	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	NCM460	Normal	Homo sapiens	CVCL_0460
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HIEC-6	Normal	Homo sapiens	CVCL_6C21
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	METTL3 acts as a critical m6A methyltransferase capable of facilitating colorectal cancer(CRC) progression, and revealed a novel mechanism by which METTL3 promotes CRC cell proliferation and invasion via stabilizing Zinc finger protein SNAI1 (SNAI1) mRNA in an m6A-dependent manner.

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[238]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transition
	cell migration
	invasion
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
In-vivo Model	All animal experiments complied with Zhongshan School of Medicine Policy on Care and Use of Laboratory Animals. For subcutaneous transplanted model, sh-control and sh-METTL3 Huh7 cells (5 × 10⁶ per mouse, n = 5 for each group) were diluted in 200 uL of PBS + 200 uL Matrigel (BD Biosciences) and subcutaneously injected into immunodeficient female mice to investigate tumor growth.
Response Summary	The upregulation of METTL3 and YTHDF1 act as adverse prognosis factors for overall survival (OS) rate of liver cancer patients. m6A-sequencing and functional studies confirm that Zinc finger protein SNAI1 (SNAI1), a key transcription factor of EMT, is involved in m6A-regulated EMT.

Family with sequence similarity 225 member A (FAM225A)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: 1.41E+00 p-value: 1.18E-04
More Results	Click to View More RNA-seq Results

Nasopharyngeal carcinoma [ICD-11: 2B6B]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[64]
Responsed Disease	Nasopharyngeal carcinoma [ICD-11: 2B6B]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation and metastasis
In-vitro Model	5-8F	Nasopharyngeal carcinoma	Homo sapiens	CVCL_C528
	6-10B	Nasopharyngeal carcinoma	Homo sapiens	CVCL_C529
	C666-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_7949
	CNE-1	Normal	Homo sapiens	CVCL_6888
	CNE-2	Nasopharyngeal carcinoma	Homo sapiens	CVCL_6889
	HK1	Nasopharyngeal carcinoma	Acipenser baerii	CVCL_YE27
	HNE-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_0308
	HONE-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_8706
	N2Tert (The human immortalized nasopharyngeal epithelial cell lines)
	NP69 (A human immortalized nasopharyngeal epithelial)
	S18	Nasopharyngeal carcinoma	Homo sapiens	CVCL_B0U9
	S26	Nasopharyngeal carcinoma	Homo sapiens	CVCL_B0UB
	SUNE1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_6946
In-vivo Model	For the tumor growth model, 1 × 10⁶ HNE1-Scrambled or HNE1-shFAM2225A 2# cells were injected into the axilla of the mice, and the tumor size was measured every 3 days.
Response Summary	Family with sequence similarity 225 member A (FAM225A) functioned as a competing endogenous RNA (ceRNA) for sponging miR-590-3p and miR-1275, leading to the upregulation of their target integrin beta-3 (ITGB3), and the activation of FAK/PI3K/Akt signaling to promote Nasopharyngeal carcinoma cell proliferation and invasion. FAM225A showed lower RNA stability after silencing of METTL3.

H19 imprinted maternally expressed transcript (H19)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	DKO-1 cell line	Homo sapiens
Treatment: METTL3 knockdown DKO-1 cell Control: DKO-1 cell		GSE182382
Regulation		logFC: -2.53E+00 p-value: 9.95E-11
More Results	Click to View More RNA-seq Results

Abnormalities of breathing [ICD-11: MD11]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[240]
Responsed Disease	Abnormalities of breathing [ICD-11: MD11]
Target Regulation	Up regulation
Cell Process	Cell viability
	Cell apoptosis
In-vitro Model	H9c2(2-1)	Normal	Rattus norvegicus	CVCL_0286
In-vivo Model	In vivo myocardial I/R injury was performed by 60 min of ligation of LAD followed by 5 h of reperfusion.
Response Summary	Either knockdown of METTL3 or METTL14 notably reversed the hypoxic preconditioning-induced enhancement of cell viability, anti-apoptosis ability, and H19 imprinted maternally expressed transcript (H19) expression.

Long intergenic non-protein coding RNA 470 (LINC00470)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HeLa cell line	Homo sapiens
Treatment: METTL3 knockdown HeLa cells Control: HeLa cells		GSE70061
Regulation		logFC: 5.89E-01 p-value: 3.48E-02
More Results	Click to View More RNA-seq Results

Malignant haematopoietic neoplasm [ICD-11: 2B33]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[73]
Responsed Disease	Chronic myeloid leukaemia [ICD-11: 2B33.2]
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	RNA stability
	Cell autophagy
In-vitro Model	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	KCL-22	Chronic myelogenous leukemia	Homo sapiens	CVCL_2091
In-vivo Model	In the control mice or ADR mice group, the parental or chemo-resistant K562 cells were infected with LV-shCtrl. In the ADR + shLINC00470 group, the chemo-resistant K562 cells were infected with LV- shLINC00470. These cells were injected, respectively, into these 5-week-old mice subcutaneously.
Response Summary	The molecular mechanism underlying the effect of Long intergenic non-protein coding RNA 470 (LINC00470) on chronic myelocytic leukaemia by reducing the PTEN stability via RNA methyltransferase METTL3, thus leading to the inhibition of cell autophagy while promoting chemoresistance in CML.

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[241]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Pathway Response	Gastric cancer			hsa05226
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	GES-1	Normal	Homo sapiens	CVCL_EQ22
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
Response Summary	Long intergenic non-protein coding RNA 470 (LINC00470)-METTL3-mediated PTEN mRNA degradation relied on the m6A reader protein YTHDF2-dependent pathway.LINC00470 served as a therapeutic target for Gastric cancer patients.

Nuclear paraspeckle assembly transcript 1 (NEAT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 1.39E+00 p-value: 3.32E-29
More Results	Click to View More RNA-seq Results

Malignant haematopoietic neoplasm [ICD-11: 2B33]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[242]
Responsed Disease	Chronic myeloid leukaemia [ICD-11: 2B33.2]
Target Regulation	Up regulation
Cell Process	Cell viability and apoptosis
In-vitro Model	BV-173	Chronic myelogenous leukemia	Homo sapiens	CVCL_0181
	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	KCL-22	Chronic myelogenous leukemia	Homo sapiens	CVCL_2091
	MEG-01	Chronic myelogenous leukemia	Homo sapiens	CVCL_0425
Response Summary	METTL3-mediated m6A modification induced the aberrant expression of Nuclear paraspeckle assembly transcript 1 (NEAT1) in chronic myelocytic leukemia. Overexpression of NEAT1 inhibited cell viability and promoted the apoptosis of chronic myelocytic leukemia cells. miR-766-5p was upregulated in CML PBMCs and abrogated the effects of NEAT1 on cell viability and apoptosis of the chronic myelocytic leukemia cells.

microRNA 186 (MIR186)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 8.42E-01 p-value: 2.96E-03
More Results	Click to View More RNA-seq Results

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[243]
Responsed Disease	Hepatoblastoma [ICD-11: 2C12.01]
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Cell aggressive
In-vitro Model	HCCLM9	Adult hepatocellular carcinoma	Homo sapiens	CVCL_A5CU
	HEK293	Normal	Homo sapiens	CVCL_0045
	Hepa 1-6	Hepatocellular carcinoma of the mouse	Mus musculus	CVCL_0327
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HuH-6	Hepatoblastoma	Homo sapiens	CVCL_4381
In-vivo Model	Cells transfected with miR-186 overexpression lentivirus (Lenti-miR-186), miR-186 inhibitor (Lenti-anti-miR-186), Lenti-miR-186 & METTL3 overexpression plasmid (Lenti-METTL3), Lenti-anti-miR-186 & METTL3 shRNA (sh-METTL3) or empty lentivirus control (Lenti-NC) were subcutaneously injected into the lower flank of nude mice.
Response Summary	microRNA 186 (MIR186)/METTL3 axis contributed to the progression of Hepatoblastoma via the Wnt/beta-catenin signalling pathway.

microRNA 221 (MIR221)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	DKO-1 cell line	Homo sapiens
Treatment: METTL3 knockdown DKO-1 cell Control: DKO-1 cell		GSE182382
Regulation		logFC: 2.60E+00 p-value: 1.63E-02
More Results	Click to View More RNA-seq Results

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[244]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Up regulation
Cell Process	Cell proliferation
In-vitro Model	EJ (Human bladder cancer cells)
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
In-vivo Model	About 1× 10⁷ cells were injected subcutaneously into the axilla of the female athymic BALB/C nude mice (4-6 weeks old, 18-22 g, five mice per group).
Response Summary	METTL3 has an oncogenic role in bladder cancer through interacting with the microprocessor protein DGCR8 and positively modulating the microRNA 221 (MIR221) process in an m6A-dependent manner.

microRNA 335 (MIR335)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Mouse testis	Mus musculus
Treatment: Mettl3 knockout mouse testis Control: Mouse testis		GSE99771
Regulation		logFC: 5.81E+00 p-value: 4.09E-06
More Results	Click to View More RNA-seq Results

Acute ischemic stroke [ICD-11: 8B11]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[245]
Responsed Disease	Acute ischemic stroke [ICD-11: 8B11]
Target Regulation	Up regulation
Cell Process	RNA maturation
	Cell apoptosis
In-vitro Model	PC-12	Lung papillary adenocarcinoma	Homo sapiens	CVCL_S979
In-vivo Model	After a median incision on the neck, the left common carotid artery (CCA), internal carotid artery (ICA), and external carotid artery (ECA) were isolated. The left CCA and the ECA were ligated.
Response Summary	METTL3-mediated m6A methylation increases the maturation of microRNA 335 (MIR335), which promotes SG formation and reduces the apoptosis level of injury neurons and cells, and provides a potential therapeutic strategy for acute ischemic stroke.

microRNA 370 (MIR370)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Embryonic stem cells	Mus musculus
Treatment: METTL3 knockout mESCs Control: Wild type mESCs		GSE156481
Regulation		logFC: -4.78E+00 p-value: 3.06E-02
More Results	Click to View More RNA-seq Results

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[56]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Pathway Response	Transcriptional misregulation in cancer			hsa05202
Cell Process	Epithelial-mesenchymal transition
	Cell autophagy
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
In-vivo Model	To create the xenograft neoplasm system, 40 male BALB/c nude mice aged 5 weeks were randomly separated into sh-NC, sh-circHPS5, sh-circHPS5+CTRL, and sh-circHPS5+SAH groups (n = 5 for each group). HCC cells were subcutaneously injected into the axilla of the nude mice.
Response Summary	In hepatocellular carcinoma, METTL3 could direct the formation of circHPS5, and specific m6A controlled the accumulation of circHPS5. YTHDC1 facilitated the cytoplasmic output of circHPS5 under m6A modification. CircHPS5 can act as a microRNA 370 (MIR370) sponge to regulate the expression of HMGA2 and further accelerate hepatocellular carcinoma cell tumorigenesis.

miR-182

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HeLa cell line	Homo sapiens
Treatment: METTL3 knockdown HeLa cells Control: HeLa cells		GSE70061
Regulation		logFC: 3.78E+00 p-value: 3.86E-02
More Results	Click to View More RNA-seq Results

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[196]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	UP regulation
In-vitro Model	WPMY-1	Normal	Homo sapiens	CVCL_3814
	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
Response Summary	METTL3 promoted cell proliferation, migration, invasion and tumorigenesis in PCa. METTL3 upregulating the level of m6A, and interacted with DGCR8 to recognize the m6A modification of pre-miR-182 to regulate its splicing and maturation and promote the high expression of miRNA.

miR-503

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: METTL3 knockdown MDA-MB-231 cells Control: MDA-MB-231 cells		GSE70061
Regulation		logFC: 1.48E+00 p-value: 8.87E-04
More Results	Click to View More RNA-seq Results

Injury of heart [ICD-11: NB31]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[246]
Responsed Disease	Myocardial injury [ICD-11: NB31.Z]
Target Regulation	Up regulation
Cell Process	Mitochondrial metabolic dysfunction
In-vivo Model	To generate an AMI mouse model, mice were anesthetised by intraperitoneal injection of sterile pentobarbital sodium at 50 mg/kg body weight.
Response Summary	Hypoxia induced rapid H3K4 methylation of the promoter of the methyltransferase-like 3 gene (METTL3) and resulted in its overexpression. METTL3 overexpression evokes N6-methyladenosine (m6A)-dependent miR-503 biogenesis in endothelial cells. In summary, this study highlights a novel endogenous mechanism wherein EVs aggravate myocardial injury during the onset of AMI via endothelial cell-secreted miR-503 shuttling.

hsa-miR-26b

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Mouse testis	Mus musculus
Treatment: Mettl3 knockout mouse testis Control: Mouse testis		GSE99771
Regulation		logFC: 6.72E+00 p-value: 1.75E-06
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[57]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Down regulation
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
In-vivo Model	Eighteen BALB/C female nude mice aged 4-5 weeks and weighing 15-18 g were randomly assigned into three groups of six mice. The MCF-7 cell lines stably transfected with sh-NC + oe-NC, sh-METTL3 + oe-NC and sh-METTL3 + oe-HMGA2 were selected for subcutaneous establishment of the BC cell line MCF-7 as xenografts in the nude mice. For this purpose, MCF-7 cell lines in the logarithmic growth stage were prepared into a suspension with a concentration of about 1 × 10⁷ cells/ml. The prepared cell suspension was injected into the left armpit of the mice, and the subsequent tumor growth was recorded.
Response Summary	Silencing METTL3 down-regulate MALAT1 and HMGA2 by sponging hsa-miR-26b, and finally inhibit EMT, migration and invasion in BC, providing a theoretical basis for clinical treatment of BC.

Cyclin-dependent kinase inhibitor 2A (CDKN2A)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 7.42E+00	GSE60213

Mature T-cell lymphoma [ICD-11: 2A90]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[247]
Responsed Disease	Mature T-cell lymphoma [ICD-11: 2A90]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
Response Summary	The decline in METTL3 levels was responsible for CTCL cell proliferation and migration,Cyclin-dependent kinase inhibitor 2A (CDKN2A) was a key regulator during this process in vitro and in vivo, and insufficient methylation modification blocked the interaction between CDKN2A and m6A reader IGF2BP2, resulting in mRNA degradation.

Cytochrome P450 2C8 (CYP2C8)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 4.67E+00	GSE60213

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[248]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Pathway Response	Drug metabolism - cytochrome P450			hsa00982
Cell Process	Drug-metabolizing
In-vitro Model	HepaRG	Hepatitis C infection	Homo sapiens	CVCL_9720
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
Response Summary	In the Hepatocellular carcinoma cells YTHDC2 promotes CYP2C8 mRNA degradation via recognizing the m6A in CYP2C8 mRNA, which is installed by METTL3/14 and removed by FTO.

Keratin, type II cytoskeletal 7 (KRT7)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.21E+00	GSE60213

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[137]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
Cell Process	Lung Metastasis
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
In-vitro Model	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
In-vivo Model	First, subcutaneous transplanted model was used to evaluate the growth of BT-549LMF3 and BT-549 cells. Cells (5 × 10⁶ per mouse, n = 5 for each group) were diluted in 200 ul PBS + 200 ul Matrigel (BD Biosciences) and subcutaneously injected into immunodeficient female mice. Second, subcutaneous transplanted model was used to evaluate the metastasis potential of BT-549LMF3 and BT-549 cells. Cells (5 × 10⁶ per mouse, n = 5 for each group) were diluted in 200 ul PBS + 200 ul Matrigel (BD Biosciences) and subcutaneously injected into immunodeficient female mice. Third, the in vivo lung metastasis model was established by injecting with BT-549, BT-549LMF3, FTO stable BT-549LMF3, sh-METTL3 BT-549LMF3, and sh-KRT7 BT-549LMF3 stable cells (1 × 10⁶ per mouse, n = 5 for each group)
Response Summary	Specifically, increased METTL3 methylated KRT7-AS at A877 to increase the stability of a KRT7-AS/Keratin, type II cytoskeletal 7 (KRT7) mRNA duplex via IGF2BP1/HuR complexes. m6A promotes breast cancer lung metastasis by increasing the stability of a KRT7-AS/KRT7 mRNA duplex and translation of KRT7.

L-glutamine amidohydrolase (GLS2)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 5.89E+00	GSE60213

Oral cavity/oesophagus/stomach in situ carcinoma [ICD-11: 2E60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[249]
Responsed Disease	Esophageal squamous cell carcinoma [ICD-11: 2B70.1]
Target Regulation	Up regulation
Cell Process	Cell migration
Cell Process	Cell invasion
In-vitro Model	HEEC cell line (Normal esophageal epithelial cell line)
	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
	TE-13	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_4463
	Eca-109	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
	EC/CUHK1	Esophageal carcinoma	Homo sapiens	CVCL_RY08
Response Summary	L-glutamine amidohydrolase (GLS2) as a downstream target of METTL3. These findings uncover METTL3/GLS2 signaling as a potential therapeutic target in antimetastatic strategies against esophageal Squamous Cell Carcinoma(ESCC).

Monocyte chemotactic and activating factor (CCL2)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 4.91E+00	GSE60213

Non-alcoholic fatty liver disease [ICD-11: DB92]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[250]
Responsed Disease	Nonalcoholic steatohepatitis [ICD-11: DB92.1]
Target Regulation	Down regulation
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Mettl3^flox/flox and Mettl3-HKO mice were fasted overnight and then injected intraperitoneally with 20 uM BODIPY FL C16 in 200 ul saline for 20 min.
Response Summary	Mechanistically, METTL3 directly binds to the promoters of the Cd36 and Monocyte chemotactic and activating factor (CCL2) genes and recruits HDAC1/2 to induce deacetylation of H3K9 and H3K27 in their promoters, thus suppressing Cd36 and Ccl2 transcription. METTL3 negatively regulates hepatic Cd36 and Ccl2 gene transcription via a histone modification pathway for protection against Nonalcoholic steatohepatitis(NASH) progression.

Multidrug resistance-associated protein 1 (MRP1/ABCC1)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.47E+00	GSE60213

Gastrointestinal stromal tumor [ICD-11: 2B5B]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[251]
Responsed Disease	Gastrointestinal stromal tumour [ICD-11: 2B5B]
Responsed Drug	Imatinib		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	GIST-T1	Gastrointestinal stromal tumor	Homo sapiens	CVCL_4976
In-vitro Model	GIST882	Gastrointestinal stromal tumor	Homo sapiens	CVCL_7044
In-vivo Model	For tumor growth assay, 4 × 10⁶ logarithmically growing GIST cells were transfected with T1S-vector, T1S-METTL3, 882S-vector, or 882S-METTL3 constructs, and subcutaneously injected in 100 ul of PBS into the flank of female nude mice(4-week-old). Mice were then randomly divided into 8 groups (n = 5 in each group): (1) injected with T1S-vector-harboring cells, and treated with imatinib (600 mg/l in drinking water); (2) injected with T1S-vector-harboring cells, and treated with imatinib (600 mg/l in drinking water) and MRP1 inhibitor (100 mg/l in drinking water); (3) injected with T1S-METTL3-harboring cells, and treated with imatinib (600 mg/l in drinking water); (4) injected with T1S-METTL3-harboring cells, and treated with imatinib (600 mg/l in drinking water) and MRP1 inhibitor (100 mg/l in drinking water); (5) injected with 882S-vector-harboring cells and treated with imatinib (600 mg/l in drinking water); (6) injected with 882S-vector-harboring cells, and treated with imatinib (600 mg/l in drinking water) and MRP1 inhibitor (100 mg/l in drinking water); (7) injected with 882S-METTL3-harboring cells, and treated with imatinib (600 mg/l in drinking water); and (8) injected with 882S-METTL3-harboring cells, and treated with imatinib (600 mg/l in drinking water) and MRP1 inhibitor (100 mg/l in drinking water).
Response Summary	METTL3, and the YTHDF1/eEF-1 complex mediate the translation of Multidrug resistance-associated protein 1 (MRP1/ABCC1) mRNA in an m6A-dependent manner to regulate the intracellular concentration of imatinib and drug resistance of gastrointestinal stromal tumor (GIST).

Protein kinase C epsilon (PRKCE)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 3.25E+00	GSE60213

Ischemic heart disease [ICD-11: BA40-BA6Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[252]
Responsed Disease	Ischemic heart disease [ICD-11: BA40-BA6Z]
Target Regulation	Down regulation
Cell Process	Pyroptosis
In-vitro Model	H9c2(2-1)	Normal	Rattus norvegicus	CVCL_0286
In-vivo Model	The thoracic cavity of rats was exposed, and the left anterior descending coronary artery was ligated with a 6-0 silk thread. Successfully surgical MI could be observed, with myocardium color fading and pulse weakening. After 30 min of ischemia, the blood flow was restored by releasing the slipknot, and then 120-min perfusion was performed. Afterward, the thoracic cavity of rats was sutured. The rats were assigned into 4 groups, with 12 rats in each group. Lentivirus packaged short hairpin (sh)-negative control (NC) and sh-METTL3 (GenePharma, Shanghai, China) were injected into the rats via tail vein 24 h before operation. The titer of lentivirus was 1?×?10⁹ TU/mL, and the injection rate was 0.2 ul/min for 10 min. Blood samples were collected 24 h after reperfusion.
Response Summary	METTL3 promoted DGCR8 binding to pri-miR-143-3p through m6A modification, thus enhancing miR-143-3p expression to inhibit Protein kinase C epsilon (PRKCE) transcription and further aggravating cardiomyocyte pyroptosis and MI/R injury.

Putative uncharacterized protein DANCR (DANCR)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 9.97E+00	GSE60213

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[253]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	SJSA-1	Osteosarcoma	Homo sapiens	CVCL_1697
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
Response Summary	METTL3 contributes to OS progression by increasing Putative uncharacterized protein DANCR (DANCR) mRNA stability via m6A modification, meaning that METTL3 is a promising therapeutic target for OS treatment.

Sphingosine kinase 2 (SPHK2)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.82E+00	GSE60213

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[190]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
Response Summary	METTL3 promotes translation of Sphingosine kinase 2 (SPHK2) mRNA via an m6A-YTHDF1-dependent manner. Functionally, SPHK2 facilitates GC cell proliferation, migration and invasion by inhibiting KLF2 expression.

Suppressor of cytokine signaling 4 (SOCS4)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.78E+00	GSE60213

Thyrotoxicosis [ICD-11: 5A02]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[225]
Responsed Disease	Graves disease [ICD-11: 5A02.0]
Target Regulation	Down regulation
In-vitro Model	PBMCs (Human peripheral blood mononuclear cells (PBMCs) are isolated from peripheral blood and identified as any blood cell with a round nucleus)
Response Summary	METTL3 knock-down experiment revealed that expressions of SOCS family members SOCS1, SOCS2, Suppressor of cytokine signaling 4 (SOCS4), SOCS5, and SOCS6 were increased after METTL3 knock-down. It indicated that METTL3 is involved in the development of Graves' disease (GD) by inducing mRNA m6A methylation modification of SOCS family members.

Suppressor of cytokine signaling 6 (SOCS6)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.24E+00	GSE60213

Thyrotoxicosis [ICD-11: 5A02]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[225]
Responsed Disease	Graves disease [ICD-11: 5A02.0]
Target Regulation	Down regulation
In-vitro Model	PBMCs (Human peripheral blood mononuclear cells (PBMCs) are isolated from peripheral blood and identified as any blood cell with a round nucleus)
Response Summary	METTL3 knock-down experiment revealed that expressions of SOCS family members SOCS1, SOCS2, SOCS4, SOCS5, and Suppressor of cytokine signaling 6 (SOCS6) were increased after METTL3 knock-down. It indicated that METTL3 is involved in the development of Graves' disease (GD) by inducing mRNA m6A methylation modification of SOCS family members.

Transforming growth factor beta-1 proprotein (TGFB1)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.56E+00	GSE60213

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[235]
Responsed Disease	Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Target Regulation	Up regulation
Pathway Response	Adherens junction			hsa04520
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
Response Summary	The expression of Transforming growth factor beta-1 proprotein (TGFB1) was up-regulated, while self-stimulated expression of TGFbeta1 was suppressed in METTL3Mut/- cells. m6A performed multi-functional roles in TGFbeta1 expression and EMT modulation, suggesting the critical roles of m6A in cancer progression regulation. Snail, which was down-regulated in Mettl3Mut/- cells, was a key factor responding to TGF-Beta-1-induced EMT.

Vasopressin V2 receptor (Avpr2/V2R)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 4.52E+00	GSE60213

Polycystic kidney disease [ICD-11: GB81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[82]
Responsed Disease	Polycystic kidney disease [ICD-11: GB81]
Target Regulation	Up regulation
In-vitro Model	mIMCD-3	Normal	Mus musculus	CVCL_0429
In-vivo Model	The clone, with one wild-type Mettl3 allele and one L1L2_Bact_P cassette inserted allele, was injected into C57BL/6 blastocysts. Mettl3-targeted mouse line was established from a germline-transmitting chimera. The chimeric mouse was crossed to C57BL/6 Flp mice to excise the neomycin resistance system.
Response Summary	Mettl3 activates the cyst-promoting c-Myc and cAMP pathways through enhanced c-Myc and Vasopressin V2 receptor (Avpr2/V2R) mRNA m6A modification and translation. Thus, Mettl3 promotes Autosomal dominant polycystic kidney disease and links methionine utilization to epitranscriptomic activation of proliferation and cyst growth.

LINC00035 (ABHD11-AS1)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 5.94E+00	GSE60213

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[254]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Up regulation
Pathway Response	Central carbon metabolism in cancer			hsa05230
In-vitro Model	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	H1299 cells were transfected with sh-ABHD11-AS1 and harvested from six-well plates, then resuspended at a density 1 × 10⁷ cells/ml. Mice were subsequently injected with 100 uL suspension at the right flank. After injection, tumor weight and length were examined every 3 days.
Response Summary	LINC00035 (ABHD11-AS1) was upregulated in NSCLC tissue specimens and cells and the ectopic overexpression was closely correlated with unfavorable prognosis of NSCLC patients.METTL3 installed the m6 A modification and enhanced ABHD11-AS1 transcript stability to increase its expression.

LOC10013.776 (AGAP2-AS1)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 6.67E+00	GSE60213

Psoriasis [ICD-11: EA90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[255]
Responsed Disease	Psoriasis [ICD-11: EA90]
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	PI3K-Akt signaling pathway			hsa04151),
Cell Process	Cell proliferation
In-vitro Model	HaCaT	Normal	Homo sapiens	CVCL_0038
	NHEK (Normal human epithelial keratinocytes)
Response Summary	METTL3 resulted in the upregulation of AGAP2-AS1 in psoriasis. LOC10013.776 (AGAP2-AS1) is upregulated in the skin tissue of psoriasis patients and m6A methylation was involved in its upregulation.

Long intergenic non-protein coding RNA 1273 (LINC01273)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 7.26E+00	GSE60213

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[256]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulation	Down regulation
In-vitro Model	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
Response Summary	Long intergenic non-protein coding RNA 1273 (LINC01273) was modified with m6A, METTL3 increased LINC01273 m6A modification, followed by LINC01273 decay in the presence of YTHDF2, a m6A 'reader'. And LINC01273 plays a key role in sorafenib resistant HCC cells.

Long intergenic non-protein coding RNA 460 (LINC00460)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 6.69E+00	GSE60213

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[176]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Cell Process	mRNA stability
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	FHC	Normal	Homo sapiens	CVCL_3688
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	Groups of HCT116-Luc-shCtrl, HCT116-Luc-shLINC00460, and HCT116-Luc-shLINC00460 + HMGA1 cells (5 × 10⁶) were injected subcutaneously into the flanks of mice correspondingly.
Response Summary	Long intergenic non-protein coding RNA 460 (LINC00460) is a novel oncogene of colorectal cancer through interacting with IGF2BP2 and DHX9 and bind to the m6A modified HMGA1 mRNA to enhance the HMGA1 mRNA stability. The N6-methyladenosine (m6A) modification of HMGA1 mRNA by METTL3 enhanced HMGA1 expression in CRC.

Maternally expressed 3 (MEG3)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 6.64E+00	GSE60213

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[257]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Down regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	THLE-3	Normal	Homo sapiens	CVCL_3804
Response Summary	Maternally expressed 3 (MEG3) regulates the expression of BTG2 through miR-544b, thus affecting the malignant behavior of hepatocellular carcinoma. METTL3 regulates the m6A modification of MEG3 and its expression.

NIFK antisense RNA 1 (NIFK-AS1)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 7.43E+00	GSE60213

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[258]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	THLE-3	Normal	Homo sapiens	CVCL_3804
In-vivo Model	For the PDX model, fresh patient HCC tissues were cut into fragments with a volume of 3 × 3 mm³ and then implanted subcutaneously into the flanks of nude mice. The mice were given sorafenib (30 mg/kg) or vehicle orally twice a week for 24 days. This procedure was approved by the Ethics Committee of Jinling Hospital.
Response Summary	Identified the lncRNA NIFK antisense RNA 1 (NIFK-AS1) as being highly expressed in hepatocellular carcinoma tissues and cells, promotes disease progression and sorafenib resistance, and showed this up-regulation resulted from METTL3-dependent m6A methylation.

Pvt1 oncogene (PVT1)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.16E+01	GSE60213

Kidney failure [ICD-11: GB6Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[146]
Responsed Disease	Kidney failure [ICD-11: GB6Z]
Target Regulation	Up regulation
In-vitro Model	NIT-1	Insulin tumor	Mus musculus	CVCL_3561
Response Summary	m6A modification is co-regulated by METTL3 and FTO in cadmium-treated cells. LncRNA-MALAT1, Pvt1 oncogene (PVT1) and m6A modification could be key nodes for cadmium-induced oxidative damage, and highlight their importance as promising preventive and therapeutic targets in cadmium toxicity.

Small nucleolar RNA host gene 3 (SNHG3)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.17E+00	GSE60213

Esophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[259]
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Responsed Drug	Pt		Investigative	Drug Info
Target Regulation	Up regulation
Cell Process	Cellular Processes
	Cell growth and death
	Cell apoptosis
In-vitro Model	Eca-9706 (Esophageal carcinoma cell line)
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
In-vivo Model	Used 1 × 10⁶ SNHG3 knocked down KY-SE150 cells and NC lentivirus to inject into the right flank of mice to generate xenografts.
Response Summary	Platinum can increase the overall m6A level of esophageal cancer. Small nucleolar RNA host gene 3 (SNHG3)/miR-186-5p, induced by platinum, was involved in regulating m6A level by targeting METTL3. miR-186-5p binds to the 3'UTR of METTL3 to inhibit its expression. Our manuscript has provided clues that regulating m6A level was a novel way to enhance the platinum efficacy.

SVIL antisense RNA 1 (SVIL-AS1)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 9.54E+00	GSE60213

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[260]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulation	Up regulation
In-vitro Model	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	A549 cells (1 × 10⁶ cells) were intraperitoneally injected into the abdomen of nude mice. Tumor length and width were measured and recorded every 4 days after inoculation. Tumor volume was calculated as 1/2 × length × width2. The tumor weight was weighed and recorded 20 days after inoculation.
Response Summary	The reduction in cell proliferation induced by SVIL antisense RNA 1 (SVIL-AS1) overexpression could be rescued by E2F1 overexpression or METTL3 knockdown. In conclusion, METTL3-induced SVIL-AS1 in LUAD, which connects m6A and lncRNA in lung cancer carcinogenesis.

X inactive specific transcript (XIST)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.31E+00	GSE60213

Ossification of spinal ligaments [ICD-11: FA83]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[261]
Responsed Disease	Ossification of spinal ligaments [ICD-11: FA83]
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis	hsa04120
Cell Process	Ubiquitination degradation
In-vitro Model	Human primary ligament fibroblasts (Ligaments were dissected from a non-ossified site)
Response Summary	METTL3 regulates ossification of the posterior longitudinal ligament via the lncRNA X inactive specific transcript (XIST)/miR-302a-3p/USP8 axis.

ZNFX1 antisense RNA 1 (ZFAS1)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 3.61E+00	GSE60213

Nasopharyngeal carcinoma [ICD-11: 2B6B]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[262]
Responsed Disease	Nasopharyngeal carcinoma [ICD-11: 2B6B]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
	Cell migration
	Cell autophagy
In-vitro Model	SUNE1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_6946
	S26	Nasopharyngeal carcinoma	Homo sapiens	CVCL_B0UB
	S18	Nasopharyngeal carcinoma	Homo sapiens	CVCL_B0U9
	NP69 (A human immortalized nasopharyngeal epithelial)
	N2Tert (The human immortalized nasopharyngeal epithelial cell lines)
	HONE-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_8706
	HNE-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_0308
	NPC/HK1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_7084
	CNE-2	Nasopharyngeal carcinoma	Homo sapiens	CVCL_6889
	CNE-1	Normal	Homo sapiens	CVCL_6888
	C666-1	Nasopharyngeal carcinoma	Homo sapiens	CVCL_7949
	6-10B	Nasopharyngeal carcinoma	Homo sapiens	CVCL_C529
In-vivo Model	Female BALB/c nude mice (ages 4-5 weeks, 18-20 g) were purchased from the Charles River Laboratories. For the tumor growth model, 1 × 10⁶ HONE-1 sh-NC or sh-ZFAS1 cells were injected into the axilla of the mice, and the tumor size was measured every 3 days. On day 30, the mice were killed, and the tumors were dissected and weighed.
Response Summary	Knockout of METTL3 can reduce the total expression of ZNFX1 antisense RNA 1 (ZFAS1). ZFAS1 is used as an oncogenic lncRNA, which can promote NPCcell proliferation, migration and tumor growth.

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[263]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
In-vivo Model	Nude mice were subjected to a subcutaneous injection of 5× 10⁶ control and ZFAS1 silencing CaSki cells suspended in 0.2 mL DMEM medium.
Response Summary	ZNFX1 antisense RNA 1 (ZFAS1) sequestered miR-647, and this RNA-RNA interaction is regulated by METLL3-mediated m6A modification in cervical cancer.

Apoptotic chromatin condensation inducer in the nucleus (ACIN1)

Target Gene

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[264]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Pathway Response	RNA degradation			hsa03018
Cell Process	RNA stability
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	End1/E6E7	Normal	Homo sapiens	CVCL_3684
In-vivo Model	2 × 10⁶ stably transfected HeLa cells were subcutaneously inoculated into the left flank of mice.
Response Summary	METTL3 interacts with IGF2BP3 to promote the mRNA stability of Apoptotic chromatin condensation inducer in the nucleus (ACIN1), the overexpression of which induces the aggressiveness of CC cells.

Class E basic helix-loop-helix protein 41 (BHLHE41)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[265]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	Cytokine-cytokine receptor interaction			hsa04060
	Chemokine signaling pathway			hsa04062
Cell Process	Cell immunity
	Cell growth
	Cell migration
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	MC-38	Mouse colon adenocarcinoma	Mus musculus	CVCL_B288
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	METTL3 knockout or control CT26 and MC38 cells were injected subcutaneously into the dorsal flank of each 4- to 6-week-old male immunocompetent BALB/c and C57BL/6 mice, respectively. Anti-Gr-1 (BE0075; Bio-X-Cell, Lebanon, NH) or immunoglobulin (Ig)G isotype control (BE0090, Bio-XCell) was given every other day via intraperitoneal injection (150 ug/mouse). SB-265610 (Tocris, Bristol, UK) or phosphate-buffered saline was administrated through intraperitoneal injections at a dosage of 2 mg/kg per day. Tumor sizes were measured every other day. To establish an orthotopic mouse model of CRC, 5- to 6-week-old male C57BL/6 mice were treated with 1.7% dextran sodium sulfate in drinking water for 5 days, and then allowed to recover for 3 days. After 24 hours of fasting, METTL3 knockout or control MC38 cells suspended in 50 ul of 1 mg/mL Matrigel-phosphate-buffered saline (Corning, Corning, NY) were instilled into the colon lumen of anesthetized mice, coated sparingly with Vaseline.
Response Summary	METTL3 promoted Class E basic helix-loop-helix protein 41 (BHLHE41) expression in m6A-dependent manner, which subsequently induced CXCL1 transcription to enhance MDSC migration in vitro. METTL3 as a potential therapeutic target for CRC immunotherapy whose inhibition reverses immune suppression through m6A-BHLHE41-CXCL1 axis.

Cytokine-responsive protein CR6 (GADD45-Gamma)

Target Gene

Endocrine glands benign cancer [ICD-11: 2F37]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[266]
Responsed Disease	Endocrine glands benign cancer [ICD-11: 2F37]
Target Regulation	Up regulation
Response Summary	METTL3 promotes tumor growth and hormone secretion by increasing expression of GNAS and Cytokine-responsive protein CR6 (GADD45-Gamma) in a m6A-dependent manner. Thus, METTL3 and the methylated RNAs constitute suitable targets for clinical treatment of Pituitary growth hormone-secreting-pituitary adenomas(GH-PAs).

E3 ubiquitin-protein ligase TRIM11 (TRIM11)

Target Gene

Nasopharyngeal carcinoma [ICD-11: 2B6B]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[14]
Responsed Disease	Nasopharyngeal carcinoma [ICD-11: 2B6B]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	ABC transporters			hsa02010
	Wnt signaling pathway			hsa04310
	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Ubiquitination degradation
In-vitro Model	CNE-1	Normal	Homo sapiens	CVCL_6888
	CNE-2	Nasopharyngeal carcinoma	Homo sapiens	CVCL_6889
In-vivo Model	A total of 2 × 10⁶ cells was mixed with 0.2 ml PBS (pH 7.4) and 30% (v/v) Matrigel matrix (BD Biosciences).
Response Summary	TRIM11 regulates nasopharyngeal carcinoma drug resistance by positively modulating the Daple/beta-catenin/E3 ubiquitin-protein ligase TRIM11 (TRIM11) signaling pathway. TRIM11 enhanced the multidrug resistance in NPC by inhibiting apoptosis in vitro and promoting cisplatin (DDP) resistance in vivo. METTL3-mediated m6A modification caused the upregulation of TRIM11 via IGF2BP2 in NPC drug-resistant cells.

Guanine nucleotide-binding protein G (GNAS)

Target Gene

Endocrine glands benign cancer [ICD-11: 2F37]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[266]
Responsed Disease	Endocrine glands benign cancer [ICD-11: 2F37]
Target Regulation	Up regulation
Response Summary	METTL3 promotes tumor growth and hormone secretion by increasing expression of Guanine nucleotide-binding protein G (GNAS) and GADD45-Gamma in a m6A-dependent manner. Thus, METTL3 and the methylated RNAs constitute suitable targets for clinical treatment of Pituitary growth hormone-secreting-pituitary adenomas(GH-PAs).

Lactate dehydrogenase A (LDHA)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[267]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	HIF-1 signaling pathway			hsa04066
Pathway Response	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glycolysis
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	For subcutaneous transplanted model, sh-control and sh-METTL3 HCT-116/5-FU cells (5 × 10⁶ per mouse) were diluted in 100ul PBS + 100 ul Matrigel (BD Biosciences, San Jose, CA, USA) and injected subcutaneously in the rear flank fat pad of the nude mice.
Response Summary	METTL3 enhances the expression of Lactate dehydrogenase A (LDHA), which catalyzes the conversion of pyruvate to lactate, to trigger glycolysis and 5-FU resistance. METTL3/LDHA axis-induced glucose metabolism is a potential therapy target to overcome 5-FU resistance in CRC cells.

Mammalian target of rapamycin complex 2 (mTORC2)

Target Gene

Herpes infection [ICD-11: 1F00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[268]
Responsed Disease	Herpes infection [ICD-11: 1F00]
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
In-vitro Model	RD	Embryonal rhabdomyosarcoma	Homo sapiens	CVCL_1649
Response Summary	METTL3 knockdown suppressed the HSV-1 intermediate early and early genes (ICP0, ICP8 and UL23) and late genes (VP16, UL44, UL49 and ICP47). The components of m6A modification machinery, particularly m6A initiator METTL3 and reader YTHDF3, would be potential important targets for combating herpes virus type 1 (HSV-1) infections.

Endometrial cancer [ICD-11: 2C76]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[94]
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulation	Down regulation
Cell Process	Cell proliferation and tumorigenicity
In-vitro Model	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293
	RL95-2	Endometrial adenosquamous carcinoma	Homo sapiens	CVCL_0505
	T HESCs	Normal	Homo sapiens	CVCL_C464
In-vivo Model	4×10⁶ HEC-1-A endometrial cancer cells (shCtrl, shMETTL3, wild-type, METTL14^+/-, or METTL14^+/- rescued with wild-type or mutant METTL14) were injected intraperitoneally into 5 week old female athymic nude mice (Foxn1^nu, Harlan; n=10 per group).
Response Summary	About 70% of endometrial tumours exhibit reductions in m6A methylation that are probably due to either this METTL14 mutation or reduced expression of METTL3. Reductions in m6A methylation lead to decreased expression of the negative AKT regulator PHLPP2 and increased expression of the positive AKT regulator Mammalian target of rapamycin complex 2 (mTORC2). these results reveal reduced m6A mRNA methylation as an oncogenic mechanism in endometrial cancer and identify m6A methylation as a regulator of AKT signalling.

Cerebrovascular diseases [ICD-11: 8B22]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[269]
Responsed Disease	Arteriovenous malformation of cerebral vessels [ICD-11: 8B22.40]
Pathway Response	Notch signaling pathway			hsa04330
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
Response Summary	The expression level of METTL3 was reduced in the larger pathological tissues of cerebral arteriovenous malformation (AVM). Moreover, knockdown of METTL3 significantly affected angiogenesis of the human endothelial cells.

Retinopathy [ICD-11: 9B71]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[270]
Responsed Disease	Retinopathy [ICD-11: 9B71]
Cell Process	Cell viability
	Cell proliferation
	Cell migration
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
In-vivo Model	Mettl3^flox/flox mice were crossed with the transgenic Cdh5-CreERT2 mice to generate the Mettl3-ecKO mice. Cdh5-Cre Mettl3^flox/flox mice received an intragastric injection of 50 ul tamoxifen (1 mg/mL) at P1-P3 and P5 for Cre activation and Mettl3 knockout. After Mettl3 knockout, the mouse pups and their nursing mothers were exposed to 75% oxygen (hyperoxia) from P7 to P12 in an incubator chamber. Then, the pups were returned to normal oxygen conditions (normoxia).
Response Summary	METTL3 knockout in vivo decreased avascular area and pathological neovascular tufts in an oxygen-induced retinopathy model and inhibited alkali burn-induced corneal neovascularization.

Platelet glycoprotein 4 (CD36)

Target Gene

Non-alcoholic fatty liver disease [ICD-11: DB92]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[250]
Responsed Disease	Nonalcoholic steatohepatitis [ICD-11: DB92.1]
Target Regulation	Down regulation
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Mettl3^flox/flox and Mettl3-HKO mice were fasted overnight and then injected intraperitoneally with 20 uM BODIPY FL C16 in 200 ul saline for 20 min.
Response Summary	Mechanistically, METTL3 directly binds to the promoters of the Platelet glycoprotein 4 (CD36) genes and recruits HDAC1/2 to induce deacetylation of H3K9 and H3K27 in their promoters, thus suppressing Cd36 and Ccl2 transcription. METTL3 negatively regulates hepatic Cd36 and Ccl2 gene transcription via a histone modification pathway for protection against Nonalcoholic steatohepatitis(NASH) progression.

Protein crumbs homolog 3 (CRB3)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[271]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	FHC	Normal	Homo sapiens	CVCL_3688
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
Response Summary	m6A and METTL3 levels were substantially elevated in colorectal carcinoma(CRC) tissues, METTL3 knockdown substantially reduced the m6A level of Protein crumbs homolog 3 (CRB3), and inhibited the degradation of CRB3 mRNA to increase CRB3 expression. METTL3 regulated the progression of CRC by regulating the m6A-CRB3-Hippo pathway.

Putative pituitary tumor-transforming gene 3 protein (PTTG3P)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[272]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell proliferation and suppression of apoptosis
In-vitro Model	FHC	Normal	Homo sapiens	CVCL_3688
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	NCM460	Normal	Homo sapiens	CVCL_0460
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	Indicated cells (1 × 10⁷) were subcutaneously injected into 4-week-old male nude mice. Tumor volume was measured every 5 days.
Response Summary	In colorectal cancer, n6-methyladenosine (m6A) subunit METTL3 increased PTTG3P expression by influencing its stability, while insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) could identify Putative pituitary tumor-transforming gene 3 protein (PTTG3P) m6A methylation status and bind to it.

RAD51-associated protein 1 (RAD51AP1)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[273]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Fluorouracil		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
Response Summary	METTL3 augmented 5?FU?induced DNA damage and overcame 5?FU?resistance in HCT?8R cells, which could be mimicked by inhibition of RAD51-associated protein 1 (RAD51AP1). The present study revealed that the METTL3/RAD51AP1 axis plays an important role in the acquisition of 5?FU resistance in CRC.

Suppressor of cytokine signaling 1 (SOCS1)

Target Gene

Thyrotoxicosis [ICD-11: 5A02]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[225]
Responsed Disease	Graves disease [ICD-11: 5A02.0]
Target Regulation	Down regulation
In-vitro Model	PBMCs (Human peripheral blood mononuclear cells (PBMCs) are isolated from peripheral blood and identified as any blood cell with a round nucleus)
Response Summary	METTL3 knock-down experiment revealed that expressions of SOCS family members Suppressor of cytokine signaling 1 (SOCS1), SOCS2, SOCS4, SOCS5, and SOCS6 were increased after METTL3 knock-down. It indicated that METTL3 is involved in the development of Graves' disease (GD) by inducing mRNA m6A methylation modification of SOCS family members.

Suppressor of cytokine signaling 5 (SOCS5)

Target Gene

Thyrotoxicosis [ICD-11: 5A02]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[225]
Responsed Disease	Graves disease [ICD-11: 5A02.0]
Target Regulation	Down regulation
In-vitro Model	PBMCs (Human peripheral blood mononuclear cells (PBMCs) are isolated from peripheral blood and identified as any blood cell with a round nucleus)
Response Summary	METTL3 knock-down experiment revealed that expressions of SOCS family members SOCS1, SOCS2, SOCS4, Suppressor of cytokine signaling 5 (SOCS5), and SOCS6 were increased after METTL3 knock-down. It indicated that METTL3 is involved in the development of Graves' disease (GD) by inducing mRNA m6A methylation modification of SOCS family members.

DBH antisense RNA 1 (Lnc_DBH-AS1)

Target Gene

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[274]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Responsed Drug	Gemcitabine		Approved	Drug Info
In-vitro Model	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	HPDE	Normal	Homo sapiens	CVCL_4376
	CFPAC-1	Cystic fibrosis	Homo sapiens	CVCL_1119
	Canpan-2 (Pancreatic cancer cell line)
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
Response Summary	DBH antisense RNA 1 (Lnc_DBH-AS1) expression in pancreatic cancer(PC) was found to be linked to the METTL3-dependent m6A methylation of the lncRNA. MechanisticallyDBH-AS1 was able to increase PC cell sensitivity to gemcitabine by sequestering miR-3163 and thus upregulating USP44 in these tumor cells.

LIFR antisense RNA 1 (LIFR-AS1)

Target Gene

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[275]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway	hsa04151
Cell Process	Cell proliferation and metastasis
Response Summary	METTL3 induced m6A hyper-methylation on the 3' UTR of LIFR antisense RNA 1 (LIFR-AS1) to enhance its mRNA stability and LIFR-AS1 could directly interact with miR-150-5p, thereby indirectly up-regulating VEGFA expressions within cells. A noval m6A-LIFR-AS1 axis promotes pancreatic cancer progression at least in part via regulation of the miR-150-5p/VEGFA axis, indicating that this regulatory axis can be a viable clinical target for the treatment of pancreatic cancer.

Long intergenic non-protein coding RNA 2598 (LINC02598/RP11)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[276]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Ubiquitination degradation
In-vitro Model	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	NCM460	Normal	Homo sapiens	CVCL_0460
Response Summary	Overexpression of METTL3 upregulates Long intergenic non-protein coding RNA 2598 (LINC02598/RP11) expression in colorectal cancer cells. Overexpression of ALKBH5 downregulates RP11 expression.

Long intergenic non-protein coding RNA 680 (LINC00680)

Target Gene

Osteoarthritis [ICD-11: FA05]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[199]
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulation	Up regulation
In-vitro Model	Chondrocytes (Chondrocytes were isolated from human cartilage and cultured)
Response Summary	m6A-mediated Long intergenic non-protein coding RNA 680 (LINC00680) regulates the proliferation and ECM degradation of chondrocytes through LINC00680/m6A/SIRT1 mRNA axis. METTL3-mediated LINC00680 accelerates osteoarthritis(OA) progression, which provides novel understanding of the role of m6A and lncRNA in OA.

Small nucleolar RNA host gene (SNHG7)

Target Gene

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[277]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Up regulation
Pathway Response	Central carbon metabolism in cancer			hsa05230
Pathway Response	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glycolysis
In-vitro Model	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	RWPE-1	Normal	Homo sapiens	CVCL_3791
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
Response Summary	METTL3-stabilized lncRNA Small nucleolar RNA host gene (SNHG7) accelerates glycolysis in PCa via SRSF1/c-Myc axis and inspires the understanding of m6A roles in lncRNA metabolism and tumor progression.

microRNA 1246 (MIR1246)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[220]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	Cell migration and invasion
In-vitro Model	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	NCM460	Normal	Homo sapiens	CVCL_0460
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
In-vivo Model	The spleen in the upper left lateral abdomen of the anesthetized mice were exposed, 10⁶ cells suspended in 20 uL phosphate-buffered saline (PBS) were injected into the distal tip of the spleen. After injection, replacing the spleen, and closing the incision.
Response Summary	METTL3/microRNA 1246 (MIR1246)/SPRED2 axis plays an important role in tumor metastasis and provides a new m6A modification pattern in Colorectal cancer development.

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[91]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	The 40 nude mice of each large group were classified into 8 small groups (n = 5) and subcutaneously injected with transfected cell suspension in the back (5 × 10⁶ cells/mL/mouse). The length and width of tumors were recorded every 4 days, and the tumor volume = (length × width²)/2. The tumor growth curve was thereby graphed. On the 28^th day of injection, mice were euthanized by neck dislocation, and the xenografts were harvested, photographed, and weighed
Response Summary	METTL3 regulates the m6A modification to promote the maturation of microRNA 1246 (MIR1246), which targets PEG3 to participate in occurrence and development of non-small cell lung cancer.

microRNA 126 (MIR126)

Target Gene

Endometriosis [ICD-11: GA10]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[278]
Responsed Disease	Endometriosis [ICD-11: GA10]
Target Regulation	Up regulation
In-vitro Model	HESC (Human endometrial stromal cells)
Response Summary	The METTL3/m6A/miR126 pathway, whose inhibition contributes to endometriosis development by enhancing cellular migration and invasion.

microRNA 1305 (MIR1305)

Target Gene

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[279]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Cell Process	Reverse splicing and biogenesis
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Mice were randomly divided into three groups, and subcutaneously injected with control, circ-ARL3-silenced and circ-ARL3&miR-1305-silenced HepG2.2.15 cells.
Response Summary	circ-ARL3 is a critical regulator in HBV-related HCC, targeting the axis of circ-ARL3/microRNA 1305 (MIR1305) can be a promising treatment for HBV+ HCC patients. HBx protein upregulated N6 -methyladenosine (m6A) methyltransferases METTL3 expression, increasing the m6A modification of circ-ARL3; then, m6A reader YTHDC1 bound to m6 A-modified of circ-ARL3 and favored its reverse splicing and biogenesis. Furthermore, circ-ARL3 was able to sponge miR-1305, antagonizing the inhibitory effects of miR-1305 on a cohort of target oncogenes, thereby promoting HBV+ HCC progression.

microRNA 150 (MIR150)

Target Gene

Pain disorders [ICD-11: 8E43]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[280]
Responsed Disease	Neuropathic Pain [ICD-11: 8E43.0]
Target Regulation	Up regulation
In-vitro Model	RN-sc (The rat neuron cell line RN-sc was purchased from ScienCell (ScienCell Research Laboratories Inc. catlog. #R1590, Carlsbad, CA).)
In-vivo Model	Based on our study design, the enrolled animals were blindingly grouped and received the following treatments: (1)Sham-NC vectors, (2)Sham-sh-METTL3, (3)Sham-sh-METTL3 + miR-150, (4)Sham-sh-METTL3 + Lv-YTHDF2, (5)Sham-sh-METTL3 + sh-BDNF, (6)Sham-anti-miR150, (7)Sham-anti-miR150+sh-BDNF, (8)SNI-Lv-METTL3, (9)SNI-Lv-METTL3 + anti-miR-150, (10)SNI-Lv-METTL3 + sh-YTHDF2, (11)SNI-Lv-METTL3 + Lv-BDNF, (12)SNI-miR150, (13)SNI-miR150+Lv-BDNF. The pain behaviors were detected in the respective time points and the expressions of METTL3 and miR-150 were determined at day 14 after the rats were sacrificed.
Response Summary	Enhanced METTL3 promoted the m6A methylation in total RNAs and inhibited neuropathic pain (NP) progression. Mechanistically, METTL3 accelerated microRNA 150 (MIR150) maturation via mediating m6A methylation of primiR-150 at locus 498, cooperating with the "m6A reader" YTHDF2. Therefore, the METTL3/miR-150/BDNF pathway is a promising therapeutic target for NP patients.

microRNA 222 (MIR222)

Target Gene

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[244]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Up regulation
Cell Process	Cell proliferation
In-vitro Model	EJ (Human bladder cancer cells)
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
In-vivo Model	About 1× 10⁷ cells were injected subcutaneously into the axilla of the female athymic BALB/C nude mice (4-6 weeks old, 18-22 g, five mice per group).
Response Summary	METTL3 has an oncogenic role in bladder cancer through interacting with the microprocessor protein DGCR8 and positively modulating the microRNA 222 (MIR222) process in an m6A-dependent manner.

microRNA 25 (MIR25)

Target Gene

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[281]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	HPDE6c7	Normal	Homo sapiens	CVCL_0P38
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	SW1990	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
In-vivo Model	Mice (five in each group) were injected subcutaneously with 0.1 ml of cell suspension containing 2 × 10⁶ cells in the back flank.
Response Summary	Cigarette smoke-induced microRNA 25 (MIR25) excessive maturation via m6A modification promotes the development and progression of pancreatic cancer. This modification is catalyzed by overexpressed methyltransferase-like 3 (METTL3) due to hypomethylation of the METTL3 promoter also caused by CSC.

microRNA 93 (MIR93)

Target Gene

Emphysema [ICD-11: CA21]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[160]
Responsed Disease	Emphysema [ICD-11: CA21]
Target Regulation	Up regulation
Pathway Response	MAPK signaling pathway	hsa04010
Response Summary	METTL3-mediated formation of EV microRNA 93 (MIR93), facilitated by m6A, is implicated in the aberrant cross-talk of epithelium-macrophages, indicating that this process is involved in the smoking-related emphysema. EV miR-93 was used as a novel risk biomarker for CS-induced emphysema. MiR-93 activated the JNK pathway by targeting dual-specificity phosphatase 2 (DUSP2), which elevated the levels of matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 12 (MMP12) and induced elastin degradation, leading to emphysema.

microRNA let-7b (MIRLET7B)

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[282]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Responsed Drug	Osimertinib		Approved	Drug Info
Pathway Response	Notch signaling pathway			hsa04330
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	H1975OR (Osimertinib resistant H1975 cells)
	HCC827OR (Osimertinib resistant HCC827 cells)
Response Summary	the participation of Metformin decreased the bindings of DNMT3a/b to the METTL3 promoter with the help of the readers of NKAP and HNRNPA2B1.the mediation of m6A formation on pri-Let-7b processing increased the mature microRNA let-7b (MIRLET7B), whose key role is to suppress the Notch signaling and to re-captivate the Osimertinib treatment.The findings open up future drug development, targeting this pathway for lung cancer patients.

microRNA let-7g (MIRLET7G)

Target Gene

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[214]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Down regulation
Cell Process	Cell differentiation and apoptosis
	Glutamine metabolism
	Apoptosis (hsa04210)
Response Summary	HBXIP up-regulates METTL3 by suppressing microRNA let-7g (MIRLET7G), in which METTL3 increased HBXIP expression forming a positive feedback loop of HBXIP/let-7g/METTL3/HBXIP, leading to accelerated cell proliferation in breast cancer.

hsa-miR-126-5p

Target Gene

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[283]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
Response Summary	METTL3 promoted the maturation of hsa-miR-126-5p via the m6A modification of pri-miR-126-5p. Finally, in vitro and in vivo experiments substantiated that silencing of METTL3 impeded the progression and tumorigenesis of ovarian cancer by impairing the miR-126-5p-targeted inhibition of PTEN and thus blocking the PI3K/Akt/mTOR pathway.

Chondropathies [ICD-11: FB82]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[198]
Responsed Disease	Chondropathies [ICD-11: FB82]
Target Regulation	Up regulation
Cell Process	RNA mature
In-vitro Model	Cartilage cells (From the cartilage tissue samples from patients)
Response Summary	Interleukin 1-beta (IL-1-beta) is an important inducer of cartilage degeneration that can induce an inflammatory cascade reaction in chondrocytes and inhibit the normal biological function of cells. METTL3 could regulate hsa-miR-126-5p maturation, we first confirmed that METTL3 can bind the key protein underlying pri-miRNA processing, DGCR8. Additionally, when METTL3 expression was inhibited, the miR-126-5p maturation process was blocked.

hsa-miR-140-3p

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[148]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Up regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
Response Summary	METTL3/SNHG1/hsa-miR-140-3p/UBE2C axis plays a crucial role in cancer progression and the immune response in non-small cell lung cancer.

hsa-miR-143-3p

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[284]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulation	Down regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	RNA splicing
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
In-vivo Model	For subcutaneous transplanted model, control and miR-143-3p stable A549 cells (5 × 10⁶ per mouse, n = 5 for each group) were diluted in 200 uL PBS + 200 uL Matrigel (BD Biosciences) and subcutaneously injected into immunodeficient mice to investigate tumor growth.
Response Summary	m6A methyltransferase Mettl3 can increase the splicing of precursor hsa-miR-143-3p to facilitate its biogenesis. The miR-143-3p/VASH1 axis in BM of lung cancers and suggests their critical roles in lung cancer pathogenesis.

Ischemic heart disease [ICD-11: BA40-BA6Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[252]
Responsed Disease	Ischemic heart disease [ICD-11: BA40-BA6Z]
Target Regulation	Up regulation
Cell Process	Pyroptosis
In-vitro Model	H9c2(2-1)	Normal	Rattus norvegicus	CVCL_0286
In-vivo Model	The thoracic cavity of rats was exposed, and the left anterior descending coronary artery was ligated with a 6-0 silk thread. Successfully surgical MI could be observed, with myocardium color fading and pulse weakening. After 30 min of ischemia, the blood flow was restored by releasing the slipknot, and then 120-min perfusion was performed. Afterward, the thoracic cavity of rats was sutured. The rats were assigned into 4 groups, with 12 rats in each group. Lentivirus packaged short hairpin (sh)-negative control (NC) and sh-METTL3 (GenePharma, Shanghai, China) were injected into the rats via tail vein 24 h before operation. The titer of lentivirus was 1?×?10⁹ TU/mL, and the injection rate was 0.2 ul/min for 10 min. Blood samples were collected 24 h after reperfusion.
Response Summary	METTL3 promoted DGCR8 binding to pri-miR-143-3p through m6A modification, thus enhancing hsa-miR-143-3p expression to inhibit PRKCE transcription and further aggravating cardiomyocyte pyroptosis and MI/R injury.

hsa-miR-146a-5p

Target Gene

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[201]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Responsed Drug	Melittin		Investigative	Drug Info
Target Regulation	Up regulation
Cell Process	miRNA maturation
	Cell apoptosis
In-vitro Model	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	EJ (Human bladder cancer cells)
	BIU-87	Human bladder cancer cells	Homo sapiens	CVCL_6881
In-vivo Model	For melittin treatment study, 4-week-old female BALB/c nude mice were subcutaneously injected with 1 × 10⁷ T24 or BIU87 cells.
Response Summary	METTL3 acts as a fate determinant that controls the sensitivity of bladder cancer cells to melittin treatment. Moreover, METTL3/hsa-miR-146a-5p/NUMB/NOTCH2 axis plays an oncogenic role in bladder cancer pathogenesis and could be a potential therapeutic target for recurrent bladder cancer treatment.

hsa-miR-181d-5p

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[88]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Fluorouracil		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vivo Model	A tumor-bearing model was established by subcutaneously injecting 100 ul HT29 cells (5×10⁶) followed by an intravenous injection of CAFs-derived exosomes (50 ug/mouse every three days) into the tail vein of the mice. An intraperitoneal injection of 5-FU (50 mg/kg, every week) was administered on day 12.
Response Summary	METTL3?dependent m6A methylation was upregulated in CRC to promote the processing of miR?181d?5p by DGCR8. This led to increased hsa-miR-181d-5p expression, which inhibited the 5?FU sensitivity of CRC cells by targeting NCALD.

hsa-miR-186-5p

Target Gene

Esophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[259]
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Responsed Drug	Pt		Investigative	Drug Info
Target Regulation	Up regulation
Cell Process	Cellular Processes
	Cell growth and death
	Cell apoptosis
In-vitro Model	Eca-9706 (Esophageal carcinoma cell line)
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
In-vivo Model	Used 1 × 10⁶ SNHG3 knocked down KY-SE150 cells and NC lentivirus to inject into the right flank of mice to generate xenografts.
Response Summary	Platinum can increase the overall m6A level of esophageal cancer. SNHG3/hsa-miR-186-5p, induced by platinum, was involved in regulating m6A level by targeting METTL3. miR-186-5p binds to the 3'UTR of METTL3 to inhibit its expression. Our manuscript has provided clues that regulating m6A level was a novel way to enhance the platinum efficacy.

hsa-miR-1914-3p

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[126]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 10⁶ lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-hsa-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.

hsa-miR-1915-3p

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[102]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Down regulation
Pathway Response	TNF signaling pathway			hsa04668
Cell Process	Cell migration
	Cell invasion
	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Response Summary	hsa-miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor KLF4. miR-1915-3p function as a tumor suppressor by targeting SET and has an anti-metastatic therapeutic potential for lung cancer treatment.

hsa-miR-193b

Target Gene

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[169]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulation	Up regulation
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
In-vivo Model	Mice were divided into two groups (n = 4/group) randomly. 3×10⁶ cells suspended in 200 uL PBS were administered via subcutaneous injection over the right flank region of nude mice. After the development of palpable tumors (average volume, 50 mm³), intratumoral injection of synthetic miR-193b, or negative control complexed with siPORT Amine transfection reagent (Ambion, USA) was given 6 times at a 4-day interval.
Response Summary	METTL3 modulates miR-193b mature process in an m6A-dependent manner. Reintroduction of hsa-miR-193b profoundly inhibits tumorigenesis of cervical cancer cells both in vivo and in vitro through CCND1 targeting.

hsa-miR-199a-5p

Target Gene

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[166]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
Response Summary	METTL3-mediated circNRIP1 exhibits oncogenic roles in osteosarcoma by regulating FOXC2 via sponging hsa-miR-199a-5p, which provides new ideas for the treatment of osteosarcoma.

hsa-miR-21-5p

Target Gene

Kidney disorders [ICD-11: GB90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[285]
Responsed Disease	Kidney disorders [ICD-11: GB90]
Target Regulation	Up regulation
Pathway Response	NF-kappa B signaling pathway			hsa04064
In-vitro Model	HK2	Normal	Acipenser baerii	CVCL_YE28
In-vivo Model	Each mouse was anaesthetized with inhaled isoflurane, and the left proximal ureter was exposed. Then, the ureter was ligated with 6-0 silk thread and severed. In the sham operation group, the left ureters of mice were exposed, but not ligated or severed. The 3rd, 7th and 14th days after surgery were the time points for killing. At each time point, a total of 10 mice in the UUO group were executed, and a total of 10 mice in the sham group were also executed to serve as controls.
Response Summary	METTL3-m6A-miR-21-5p-SPRY1/ERK/NF-kB axis in obstructive renal fibrosis and provides a deeper understanding of renal fibrosis.

hsa-miR-221-3p

Target Gene

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[22]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulation	Up regulation
Cell Process	Cell growth and death
	Cell apoptosis
In-vitro Model	ADR-resistant MCF-7 (MCF-7/ADR) cells (Human breast cancer doxorubicin-resistant cell line)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
In-vivo Model	Cell suspensions (2 × 10⁶ cells/mL) made with MCF-7/ADR cells stably expressing METTL3 and/or miR-221-3p inhibitor were subcutaneously implanted into each mouse. One week later, xenografted mice were injected with 0.1 mL ADR (25 mg/kg, intraperitoneal injection) twice a week.
Response Summary	METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating hsa-miR-221-3p maturation in a m6A-dependent manner. METTL3 knockdown was shown to reduce the expression of miR-221-3p by reducing pri-miR-221-3p m6A mRNA methylation, reducing the expression of MDR1 and BCRP, and inducing apoptosis. Identified the METTL3/miR-221-3p/HIPK2/Che-1 axis as a novel signaling event that will be responsible for resistance of BC cells to ADR.

hsa-miR-222-3p

Target Gene

Thyroid Cancer [ICD-11: 2D10]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[107]
Responsed Disease	Thyroid Cancer [ICD-11: 2D10]
Target Regulation	Up regulation
Response Summary	Silencing METTL3 suppresses hsa-miR-222-3p expression and thus stimulates STK4 expression, thereby repressing the malignancy and metastasis of Thyroid Carcinoma.

hsa-miR-25-3p

Target Gene

Diabetes [ICD-11: 5A10-5A14]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[286]
Responsed Disease	Diabetes [ICD-11: 5A10-5A14]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell viability
	Cell apoptosis
In-vitro Model	ARPE-19	Normal	Homo sapiens	CVCL_0145
Response Summary	METTL3 involves in the pathogenesis of diabetic retinopathy (DR). Both METTL3 mRNA and hsa-miR-25-3p were low-expressed in the peripheral venous blood samples of diabetes mellitus (DM) patients compared to normal volunteers, and high-glucose inhibited METTL3 and miR-25-3p expressions in RPE cells. Overexpression of METTL3 attenuates high-glucose induced RPE cell pyroptosis by regulating miR-25-3p/PTEN/Akt signaling cascade through DGCR8.

Retinopathy [ICD-11: 9B71]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[286]
Responsed Disease	Diabetic retinopathy [ICD-11: 9B71.0]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell viability
	Cell apoptosis
In-vitro Model	ARPE-19	Normal	Homo sapiens	CVCL_0145
Response Summary	METTL3 involves in the pathogenesis of diabetic retinopathy (DR). Both METTL3 mRNA and hsa-miR-25-3p were low-expressed in the peripheral venous blood samples of diabetes mellitus (DM) patients compared to normal volunteers, and high-glucose inhibited METTL3 and miR-25-3p expressions in RPE cells. Overexpression of METTL3 attenuates high-glucose induced RPE cell pyroptosis by regulating miR-25-3p/PTEN/Akt signaling cascade through DGCR8.

hsa-miR-29a-3p

Target Gene

Acute respiratory distress syndrome [ICD-11: CB00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[287]
Responsed Disease	Acute respiratory distress syndrome [ICD-11: CB00]
Target Regulation	Up regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	All the mice were randomly divided into three groups: the normal saline group (NS), the lipopolysaccharide + negative control group (LPS + NC), and the LPS + miR-29a-3p agomir group (LPS + Agomir).
Response Summary	The knockout of methyltransferase 3 (N6-adenosine-methyltransferase complex catalytic subunit) removed the m6A modification of hsa-miR-29a-3p and reduced miR-29a-3p expression. These findings suggest that miR-29a-3p is a potential target that can be manipulated for ALI/ARDS.

hsa-miR-31-5p

Target Gene

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[157]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell cycle
In-vitro Model	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	HCC1806	Breast squamous cell carcinoma	Homo sapiens	CVCL_1258
	MCF-10A	Normal	Homo sapiens	CVCL_0598
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MDA-MB-453	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	ZR-75-1	Invasive breast carcinoma	Homo sapiens	CVCL_0588
In-vivo Model	Twelve female BALB/c nude mice (aged 4 weeks, 18-22g) were randomly divided into 2 groups. Stable circMETTL3-expression SUM1315 cells or control cells (1×10⁶ cells in 0.1 mL PBS) was subcutaneously injected into mammary fat pads of the mice and the growth of tumors was followed up every week. Tumor volume was measured every week using a caliper, calculated as (length × width²)/2. After 4 weeks, mice were sacrificed and checked for final tumor weight.
Response Summary	circMETTL3 promotes breast cancer progression through circMETTL3/hsa-miR-31-5p/CDK1 axis.

hsa-miR-320b

Target Gene

Oral cavity/oesophagus/stomach in situ carcinoma [ICD-11: 2E60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[197]
Responsed Disease	Esophageal squamous cell carcinoma [ICD-11: 2B70.1]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Epithelial-mesenchymal transition
In-vitro Model	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
	KYSE-30	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1351
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
	HET-1A	Normal	Homo sapiens	CVCL_3702
	CVCL_E307	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_E307
	Eca-109	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
In-vivo Model	Luciferase-labeled KYSE150 cells (5 × 10⁶) were inoculated into the footpads of BALB/c nude mice (4-5 weeks old, 18-20 g) to establish the popliteal lymphatic metastasis model.
Response Summary	METTL3 could interact with DGCR8 protein and positively modulate pri-miR-320b maturation process in an N6-methyladenosine (m6A)-dependent manner. Therefore, our findings uncover a VEGF-C-independent mechanism of exosomal and intracellular hsa-miR-320b-mediated LN metastasis and identify miR-320b as a novel predictive marker and therapeutic target for LN metastasis in ESCC.

hsa-miR-34a

Target Gene

Aortic aneurysm or dissection [ICD-11: BD50]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[288]
Responsed Disease	Abdominal aortic aneurysm [ICD-11: BD50.4]
Target Regulation	Up regulation
In-vitro Model	VSMC (Human aortic vascular smooth muscle cells)
In-vivo Model	Male C57BL/6J mice were anesthetized with an intraperitoneal injection of pentobarbital (40 mg/kg). The abdominal aorta between the renal arteries and the bifurcation of the iliac arteries was disassociated from the surrounding structures. Video microscopy was used to assay the diameter of the aorta in triplicate. After the measurements were taken, a small piece of gauze dipped in 0.5 mol/L CaCl2 was spread perivascularly onto the aortic passage for 15 min. Control mice received substitute treatment with NaCl (0.9%)-soaked gauze for 15 min. Then, the aorta was rinsed with 0.9% sterile saline, and the incision was sutured. After 3 or 6 weeks, all the animals were sacrificed, and the aortas were harvested for further analysis.
Response Summary	METTL3/m6A-mediated hsa-miR-34a maturation in AAA formation and provide a novel therapeutic target and diagnostic biomarker for AAA treatment.

hsa-miR-375-3p

Target Gene

Atherosclerosis [ICD-11: BD40]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[289]
Responsed Disease	Atherosclerosis [ICD-11: BD40.Z]
Target Regulation	Up regulation
Pathway Response	Focal adhesion	hsa04510
In-vitro Model	MOVAS (Mouse aortic vascular smooth muscle cell lines)
In-vivo Model	The normal group consisted of C57BL/6J mice on normal diet and the HFD group consisted of ApoE C57BL/6J mice on HFD (containing 10% lard oil, 4% milk powder, 2% cholesterol, and 0.5% sodium cholate). Four weeks after HFD feeding, the mice were injected with 200 ul lentivirus containing 1 × 10^-/--/-8 TU (lentivirus carrying sh-METTL3 or sh-NC; designed and constructed by GENCHEM (Shanghai, China)) via tail vein. Six weeks after transfection, all mice were euthanized by a tail vein injection of 200 mg/kg pentobarbital sodium.
Response Summary	Silencing METTL3 inhibited m6A level and decreased the binding of DGCR8 to pri-miR-375 and further limited hsa-miR-375-3p expression. METTL3-mediated m6A modification promoted VSMC phenotype transformation and made Atherosclerosis (AS) plaques more vulnerable via the miR-375-3p/PDK1 axis.

hsa-miR-380-3p

Target Gene

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[290]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	HPDE	Normal	Homo sapiens	CVCL_4376
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	Capan-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0026
	SW1990	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
In-vivo Model	The PC cell line PANC1 was subcutaneously injected into the dorsal flank of the mice at the concentration of 1 × 10⁶ cells per mouse.
Response Summary	hsa-miR-380-3p was enriched with m6A modifications, and elimination of m6A modifications by deleting METTL3 and METTL14 synergistically suppressed miR-380-3p expressions in pancreatic cancer cells.

hsa-miR-422a

Target Gene

Unspecific body region injury [ICD-11: ND56]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[291]
Responsed Disease	Unspecific body region injury [ICD-11: ND56]
Target Regulation	Up regulation
Cell Process	Neuronal cell apoptosis
In-vitro Model	SH-SY5Y	Neuroblastoma	Homo sapiens	CVCL_0019
Response Summary	Oxygen glucose deprivation/re-oxygenation (OGD/R) induces neuronal injury via mechanisms that are believed to mimic the pathways associated with brain ischemia. METTL3 shRNA reversed OGD/R-induced Lnc-D63785 m6A methylation to decrease hsa-miR-422a accumulation.

hsa-miR-582-3p

Target Gene

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[292]
Responsed Disease	Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
In-vitro Model	TFK-1	Cholangiocarcinoma	Homo sapiens	CVCL_2214
	RBE	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_4896
	HuH-28	Cholangiocarcinoma	Homo sapiens	CVCL_2955
	HuCC-T1	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_0324
	HIBEpic (Human intrahepatic bile duct epithelial cells)
	CC-LP-1	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_0205
In-vivo Model	To detect the effect of NKILA on CAA growth, 5 × 10⁶ control and NKILA-depleted HuCCT1 cells (n = 4 per group) were subcutaneously injected into male BALB/c nude mice (4-6 weeks old).
Response Summary	NKILA physically interacted with and suppressed hsa-miR-582-3p, which was regulated by METTL3-mediated N6 -methyladenosine (m6A) modification. YAP1 was a target of NKILA via miR-582-3p and NKILA functioned partially via YAP1 in CCA.

hsa-miR-589-5p

Target Gene

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[293]
Responsed Disease	Liver cancer [ICD-11: 2C12]
Target Regulation	Up regulation
Pathway Response	Adherens junction			hsa04520
Cell Process	Cell migration
Cell Process	Cell invasion
In-vitro Model	THLE-2	Normal	Homo sapiens	CVCL_3803
	SNU-423	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0366
	SNU-387	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0250
	SNU-182	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0090
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	The mice were fed in an SPF environment (cycle of 12-h light and 12-h dark) with a free diet. All the mice were adaptively fed for 5 days before experiments and randomly divided into the following four groups: the siNC+MC group (n = 10), the METTL3 siRNA1+MC group (n = 10), siNC+M group (n = 10) and the METTL3 siRNA1+M group (n = 10). Then, the right forelimb of mice in the siNC+MC group was subcutaneously injected with 100 uL PBS containing 1 × 10⁶ SK-Hep1 cells co-transfected with siNC and MC; the right forelimb of mice in the METTL3 siRNA1+MC group was subcutaneously injected with 100 uL PBS containing 1 × 10⁶ SK-Hep1 cells co-transfected with METTL3 siRNA1 and MC; the right forelimb of mice in the siNC+M group was subcutaneously injected with 100 uL PBS containing 1 × 10⁶ SK-Hep1 cells co-transfected with siNC and M; the right forelimb of mice in the METTL3 siRNA1+M group was subcutaneously injected with 100 uL PBS containing 1 × 10⁶ SK-Hep1 cells co-transfected with METTL3 siRNA1 and M.
Response Summary	METTL3 up-regulated the expression of hsa-miR-589-5p and promoted the maturation of miR-589-5p. Overexpressed miR-589-5p and METTL3 promoted the viability, migration and invasion of liver cancer cells.

hsa-miR-671-5p

Target Gene

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[21]
Responsed Disease	Glioma [ICD-11: 2A00.0]
Target Regulation	Up regulation
In-vitro Model	T98G	Glioblastoma	Homo sapiens	CVCL_0556
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	LN-18	Glioblastoma	Homo sapiens	CVCL_0392
	HEB (human normal glial cell line HEB were obtained from Tongpai (Shanghai) biotechnology co., LTD (Shanghai, China))
	A-172	Glioblastoma	Homo sapiens	CVCL_0131
Response Summary	METTL3-mediated m6A modification upregulated circDLC1 expression, and circDLC1 promoted CTNNBIP1 transcription by sponging hsa-miR-671-5p, thus repressing the malignant proliferation of glioma.

hsa-miR-766-5p

Target Gene

Malignant haematopoietic neoplasm [ICD-11: 2B33]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[242]
Responsed Disease	Chronic myeloid leukaemia [ICD-11: 2B33.2]
Target Regulation	Up regulation
Cell Process	Cell viability and apoptosis
In-vitro Model	BV-173	Chronic myelogenous leukemia	Homo sapiens	CVCL_0181
	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	KCL-22	Chronic myelogenous leukemia	Homo sapiens	CVCL_2091
	MEG-01	Chronic myelogenous leukemia	Homo sapiens	CVCL_0425
Response Summary	METTL3-mediated m6A modification induced the aberrant expression of NEAT1 in chronic myelocytic leukemia. Overexpression of NEAT1 inhibited cell viability and promoted the apoptosis of chronic myelocytic leukemia cells. hsa-miR-766-5p was upregulated in CML PBMCs and abrogated the effects of NEAT1 on cell viability and apoptosis of the chronic myelocytic leukemia cells.

hsa-miR-873-5p

Target Gene

Diseases of the urinary system [ICD-11: GC2Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[294]
Responsed Disease	Diseases of the urinary system [ICD-11: GC2Z]
Target Regulation	Up regulation
Cell Process	Oxidative stress and apoptosis
In-vitro Model	mRTEC (Mouse renal tubular epithelial cells)
Response Summary	METTL3 interacts with the microprocessor protein DGCR8 and positively modulates hsa-miR-873-5p mature process in an m6A-dependent manner.METTL3/m6A in colistin-induced nephrotoxicity and provide a new insight on m6A modification in drug induced toxicity.

hsa_circ_0000677

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[295]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
In-vitro Model	NCM460	Normal	Homo sapiens	CVCL_0460
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
In-vivo Model	For the tumor xenograft, mice were randomly divided into three groups with four mice for each group. Then, 1 × 10⁶ cells after indicated treatment were harvested and resuspended in 50 ul of PBS. Then the cells were subcutaneously injected into the right front flank of each mouse.
Response Summary	hsa_circ_0000677 and its downstream target ABCC1 were upregulated in CRC cells, induced by the METTL3-mediated m6 A modification of circ_0000677 and SUMO1-mediated SUMOylation of METTL3. This work provided a new strategy for the therapeutic treatment of CRC.

mmu-miR-365-3p

Target Gene

Chronic pain [ICD-11: MG30]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[296]
Responsed Disease	Chronic pain [ICD-11: MG30]
Target Regulation	Up regulation
Pathway Response	MicroRNAs in cancer	hsa05206
Cell Process	RNA stability
Response Summary	METTL3 positively modulated the mmu-miR-365-3p processing in a microprocessor protein DiGeorge critical region 8-dependent manner.METTL3-mediated m6A modification in nociceptive sensitization and provide a novel perspective on m6A modification in the development of Inflammatory pain.

mmu-miR-7212-5p

Target Gene

Unspecific body region injury [ICD-11: ND56]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[297]
Responsed Disease	Unspecific body region injury [ICD-11: ND56]
Target Regulation	Up regulation
Cell Process	Cell differentiation
In-vitro Model	MC3T3-E1	Normal	Mus musculus	CVCL_0409
In-vivo Model	A longitudinal incision was made on the skin and the muscles were separated to expose the femur. A transverse osteotomy was performed in the mid-diaphysis of the femur, and the bones were stabilized by inserting a 23-gauge intramedullary needle. Equal amounts (100 uL) of phosphate-buffered saline (PBS), plasmid METTL3 and agomiR-7212-5p (10 mg/kg body weight) were locally injected into the femoral fracture site.
Response Summary	Down-regulation of METTL3 promotes osteogenic processes both in vitro and in vivo, and this effect is recapitulated by the suppression of mmu-miR-7212-5p maturation. miR-7212-5p inhibits osteoblast differentiation in MC3T3-E1 cells by targeting FGFR3.

hsa_circ_0004771 (circNRIP1)

Target Gene

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[166]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
Response Summary	METTL3-mediated hsa_circ_0004771 (circNRIP1) exhibits oncogenic roles in osteosarcoma by regulating FOXC2 via sponging miR-199a, which provides new ideas for the treatment of osteosarcoma.

hsa_circ_0008399

Target Gene

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[298]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Protein export			hsa03060
Cell Process	Eukaryotic translation
	Cell apoptosis
In-vitro Model	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
	RT-4	Bladder carcinoma	Homo sapiens	CVCL_0036
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
In-vivo Model	Chose 4-week-old female BALB/c nude mice for tumor xenograft experiments, which randomly were divided into four groups (n = 5 per group). Bladder cancer cells (3 × 10⁶) were subcutaneously injected into the right axilla of the nude mice.
Response Summary	Circ0008399 bound WTAP to promote formation of the WTAP/METTL3/METTL14 m6A methyltransferase complex, reduce cisplatin sensitivity in bladder cancer, implicating the potential therapeutic value of targeting this axis.

hsa_circ_0008542

Target Gene

Diseases of the musculoskeletal system [ICD-11: FC0Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[299]
Responsed Disease	Diseases of the musculoskeletal system [ICD-11: FC0Z]
Target Regulation	Up regulation
Cell Process	RNA stability
In-vitro Model	RAW 264.7	Mouse leukemia	Mus musculus	CVCL_0493
In-vitro Model	MC3T3-E1	Normal	Mus musculus	CVCL_0409
In-vivo Model	circ_0008542, where rats were injected with exosomes containing circ_0008542 into the tail vein for 8 weeks.
Response Summary	METTL3 acts on the m6A functional site of 1956 bp in hsa_circ_0008542. RNA demethylase ALKBH5 inhibits the binding of circ_0008542 with miRNA-185-5p to correct the bone resorption process.

hsa_circ_0021427 (circHPS5)

Target Gene

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[56]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Pathway Response	Transcriptional misregulation in cancer			hsa05202
Cell Process	Epithelial-mesenchymal transition
	Cell autophagy
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
In-vivo Model	To create the xenograft neoplasm system, 40 male BALB/c nude mice aged 5 weeks were randomly separated into sh-NC, sh-circHPS5, sh-circHPS5+CTRL, and sh-circHPS5+SAH groups (n = 5 for each group). HCC cells were subcutaneously injected into the axilla of the nude mice.
Response Summary	In hepatocellular carcinoma, METTL3 could direct the formation of hsa_circ_0021427 (circHPS5), and specific m6A controlled the accumulation of circHPS5. YTHDC1 facilitated the cytoplasmic output of circHPS5 under m6A modification. CircHPS5 can act as a miR-370 sponge to regulate the expression of HMGA2 and further accelerate hepatocellular carcinoma cell tumorigenesis.

hsa_circ_0029589

Target Gene

Acute coronary syndrome [ICD-11: BA4Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[300]
Responsed Disease	Acute coronary syndrome [ICD-11: BA4Z]
Target Regulation	Down regulation
Cell Process	Macrophage pyroptosis
In-vitro Model	CD14 + cells (CD14+ cells from human peripheral blood)
Response Summary	The relative RNA expression level of hsa_circ_0029589 in macrophages was decreased, whereas the N6-methyladenosine (m6A) level of hsa_circ_0029589 and the expression of m6A methyltransferase METTL3 were validated to be significantly elevated in macrophages in patients with acute coronary syndrome.

hsa_circ_0058493

Target Gene

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[301]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Pathway Response	Hepatocellular carcinoma			hsa05225
Cell Process	Cell growth and metastasis
In-vitro Model	BEL-7404	Endocervical adenocarcinoma	Homo sapiens	CVCL_6568
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	Groups of HCT116-Luc-shCtrl, HCT116-Luc-shLINC00460, and HCT116-Luc-shLINC00460 + HMGA1 cells (5 × 10⁶) were injected subcutaneously into the flanks of mice correspondingly.
Response Summary	In hepatocellular carcinoma, hsa_circ_0058493 contained m6A methylation sites and that METTL3 mediated the degree of methylation modification of hsa_circ_0058493. YTHDC1 could bind to hsa_circ_0058493 and promote its intracellular localization from the nucleus to the cytoplasm.

hsa_circ_0081609 (circCUX1)

Target Gene

Hypopharyngeal cancer [ICD-11: 2B6D]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[302]
Responsed Disease	Hypopharyngeal squamous cell carcinoma [ICD-11: 2B6D.0]
Target Regulation	Up regulation
In-vitro Model	CLA-27 cell line (The head and neck tumor cell lines)
	HOK	Normal	Hexagrammos otakii	CVCL_YE19
	SAS	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1675
	SCC-15	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1681
	SCC-4	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1684
	SCC-9	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1685
	Tca8113	Endocervical adenocarcinoma	Homo sapiens	CVCL_6851
Response Summary	METTL3-mediated m6A modification plays a key role in stabilizing the expression of hsa_circ_0081609 (circCUX1), thereby inhibiting the expression of caspase 1 and conferring the radiotherapy resistance of hypopharyngeal squamous cell carcinoma.

hsa_circ_0092493 (circ_ARL3)

Target Gene

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[279]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Cell Process	Reverse splicing and biogenesis
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Mice were randomly divided into three groups, and subcutaneously injected with control, circ-ARL3-silenced and circ-ARL3&miR-1305-silenced HepG2.2.15 cells.
Response Summary	hsa_circ_0092493 (circ_ARL3) is a critical regulator in HBV-related HCC, targeting the axis of circ-ARL3/miR-1305 can be a promising treatment for HBV+ HCC patients. HBx protein upregulated N6 -methyladenosine (m6A) methyltransferases METTL3 expression, increasing the m6A modification of circ-ARL3; then, m6A reader YTHDC1 bound to m6 A-modified of circ-ARL3 and favored its reverse splicing and biogenesis. Furthermore, circ-ARL3 was able to sponge miR-1305, antagonizing the inhibitory effects of miR-1305 on a cohort of target oncogenes, thereby promoting HBV+ HCC progression.

Circ_1662

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[124]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cell invasion
	Cell migration
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In-vivo Model	BALB/c nude mice (4 weeks old) were acquired from Vital River Laboratory (Beijing, China). HCT116 cells with stable circ1662 expression (2 × 10⁶ in 100 L of PBS) were injected via the tail vein. After 45 days, the mice were sacrificed. The lung metastatic carcinoma specimens were processed into paraffin-embedded sections for subsequent H&E staining and IHC.
Response Summary	METTL3-induced Circ_1662 promoted colorectal cancer cell invasion and migration by accelerating YAP1 nuclear transport. Circ1662 enhanced CRC invasion and migration depending on YAP1 and SMAD3. This result implies that circ1662 is a new prognostic and therapeutic marker for CRC metastasis.

Circ_ASK1

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[303]
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Responsed Drug	Gefitinib		Approved	Drug Info
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
	SK-LU-1	Lung adenocarcinoma	Homo sapiens	CVCL_0629
	NCI-H1993	Lung adenocarcinoma	Homo sapiens	CVCL_1512
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	16HBE14o-	Normal	Homo sapiens	CVCL_0112
In-vivo Model	Established a xenograft model in BALB/c nude mice by inoculating HCC827-GR cells transfected with the constructs for circASK1 silencing, ASK1-272a.a overexpression and ASK1-272a.a overexpression/circASK1 knockdown
Response Summary	Increased YTHDF2-mediated endoribonucleolytic cleavage of m6A-modified Circ_ASK1 accounts for its downregulation in gefitinib-resistant cells. Either METTL3 silencing or YTHDF2 silencing suppressed the decay of circASK1 in HCC827-GR cells. This study provides a novel therapeutic target to overcome gefitinib resistance in LUAD patients.

Circ_DLC1

Target Gene

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[21]
Responsed Disease	Glioma [ICD-11: 2A00.0]
Target Regulation	Up regulation
In-vitro Model	T98G	Glioblastoma	Homo sapiens	CVCL_0556
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	LN-18	Glioblastoma	Homo sapiens	CVCL_0392
	HEB (human normal glial cell line HEB were obtained from Tongpai (Shanghai) biotechnology co., LTD (Shanghai, China))
	A-172	Glioblastoma	Homo sapiens	CVCL_0131
Response Summary	METTL3-mediated m6A modification upregulated Circ_DLC1 expression, and circDLC1 promoted CTNNBIP1 transcription by sponging miR-671-5p, thus repressing the malignant proliferation of glioma.

Circ_IGF2BP3

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[304]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Up regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	SW900	Lung squamous cell carcinoma	Homo sapiens	CVCL_1731
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1703	Lung squamous cell carcinoma	Homo sapiens	CVCL_1490
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	16HBE14o-	Normal	Homo sapiens	CVCL_0112
In-vivo Model	A total of 10⁶ LLC cells transfected with the following constructs were injected subcutaneously into C57BL/6 mice.
Response Summary	In non-small-cell lung carcinoma, METTL3 mediates the N6-methyladenosine (m6A) modification of Circ_IGF2BP3 and promotes its circularization in a manner dependent on the m6A reader protein YTHDC1.

LCAT3

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[47]
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Target Regulation	Up regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0608
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HOP-62	Lung adenocarcinoma	Homo sapiens	CVCL_1285
In-vivo Model	For the in vivo tumorigenicity assay, female BALB/c nude mice (ages 4-5 weeks) were randomly divided into two groups (n = 6/group). Calu1 cells (4 × 10⁶) that had been stably transfected with sh-LCAT3 or scramble were implanted subcutaneously into the nude mice. Tumor growth was measured after one week, and tumor volumes were calculated with the following formula: Volume (cm³) = (length × width²)/2. After four weeks, the mice were euthanized, and the tumors were collected and weighed. For the in vivo tumor invasion assay, 1.2 × 10⁶ scramble or shLCAT3 cells were injected intravenously into the tail vein of nude mice (n = 6/group). 1.5 mg luciferin (Gold Biotech, St Louis, MO, USA) was administered once a week for 4 weeks, to monitor metastases using an IVIS@ Lumina II system (Caliper Life Sciences, Hopkinton, MA, USA).
Response Summary	LCAT3 upregulation is attributable to N6-methyladenosine (m6A) modification mediated by methyltransferase like 3 (METTL3), leading to LCAT3 stabilization. LCAT3 as a novel oncogenic lncRNA in the lung, and validated the LCAT3-FUBP1-MYC axis as a potential therapeutic target for lung adenocarcinomas.

Lnc_D63785

Target Gene

Unspecific body region injury [ICD-11: ND56]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[291]
Responsed Disease	Unspecific body region injury [ICD-11: ND56]
Target Regulation	Down regulation
Cell Process	Neuronal cell apoptosis
In-vitro Model	SH-SY5Y	Neuroblastoma	Homo sapiens	CVCL_0019
Response Summary	Oxygen glucose deprivation/re-oxygenation (OGD/R) induces neuronal injury via mechanisms that are believed to mimic the pathways associated with brain ischemia. METTL3 shRNA reversed OGD/R-induced Lnc_D63785 m6A methylation to decrease miR-422a accumulation.

miR-17-92

Target Gene

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[305]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Responsed Drug	Everolimus		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	miRNA maturation
In-vitro Model	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
In-vivo Model	For subcutaneous xenograft models, 0.1 mL of cell suspension containing 10⁶ cells were injected subcutaneously into the right flank of mice (n = 6 for each group).
Response Summary	In gastric cancer, m6A facilitated processing of pri-miR-17-92 into the miR-17-92 cluster through an m6A/DGCR8-dependent mechanism. METTL3-high tumors showed preferred sensitivity to an mTOR inhibitor, everolimus.

p-P70

Target Gene

Renal cell carcinoma [ICD-11: 2C90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[109]
Responsed Disease	Renal cell carcinoma [ICD-11: 2C90]
Target Regulation	Down regulation
Cell Process	Epithelial-to-mesenchymal transition
Cell Process	Arrest cell cycle at G0/G1 phase
In-vitro Model	ACHN	Papillary renal cell carcinoma	Homo sapiens	CVCL_1067
	Caki-1	Clear cell renal cell carcinoma	Homo sapiens	CVCL_0234
	Caki-2	Papillary renal cell carcinoma	Homo sapiens	CVCL_0235
	HK2	Normal	Acipenser baerii	CVCL_YE28
In-vivo Model	Cells (5×10⁶ cells in 200 uL) were suspended with 100 uL PBS and 100 uL Matrigel Matrix, and injected subcutaneously into the left armpit of each mouse.
Response Summary	Knockdown of METTL3 could obviously promote cell proliferation, migration and invasion function, and induce G0/G1 arrest,METTL3 acts as a novel marker for tumorigenesis, development and survival of RCC. Knockdown of METTL3 promoted changes in pI3K/AKT/mTOR markers' expression with a gain in p-PI3k, p-AKT, p-mTOR and p-P70, and a loss of p-4EBP1.

PncRNA-D

Target Gene

Liposarcoma [ICD-11: 2B59]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[306]
Responsed Disease	Liposarcoma [ICD-11: 2B59]
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell cycle
In-vitro Model	HAP1	Chronic myelogenous leukemia	Homo sapiens	CVCL_Y019
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
In-vivo Model	,
Response Summary	Knockdown of METTL3 prolonged the half-life of PncRNA-D, and among the known m6A recognition proteins, YTHDC1 was responsible for binding m6A of pncRNA-D Knockdown of METTL3 or YTHDC1 also enhanced the interaction of pncRNA-D with TLS, and results from RNA pulldown assays implicated YTHDC1 in the inhibitory effect on the TLS-pncRNA-D interaction.

pri-miR-143

Target Gene

Acute myocardial infarction [ICD-11: BA41]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[307]
Responsed Disease	Acute myocardial infarction [ICD-11: BA41]
Target Regulation	Down regulation
In-vitro Model	neonatal ventricular myocytes (Mouse hearts were enzymatically digested to acquire the primary neonatal ventricular myocytes)
	AC16 [Human hybrid cardiomyocyte]	Normal	Homo sapiens	CVCL_4U18
Response Summary	METTL3 deficiency contributes to heart regeneration after MI via METTL3-pri-miR-143-(miR-143)-Yap/Ctnnd1 axis.

pri-miR-221

Target Gene

Cardiomegaly [ICD-11: BC45]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[308]
Responsed Disease	Cardiomegaly [ICD-11: BC45]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway	hsa04310
In-vitro Model	NRCMs (Primary neonatal rat cardiomyocytes (NRCMs)NRCMs were prepared from the hearts of 2- to 3-day-old SD rats according to the following protocol)
In-vivo Model	The pump was prefilled with Ang-II or saline and then incubated in sterile saline at 37 ℃ for 48 h. After the mice were anesthetized with 3.0% isoflurane mixed with oxygen, an incision was made on the back skin of the mice, and the pump was implanted into the subcutaneous area, followed by suturing the incision. After the operation, the mice were given buprenorphine (0.1 mg/kg) to reach analgesia. Finally, the regaining consciousness mice were returned to cages and fed until the end of the experiment.
Response Summary	METTL3 positively modulates the pri-miR-221/222 maturation process in an m6A-dependent manner and subsequently activates Wnt/Beta-catenin signaling by inhibiting DKK2, thus promoting Ang-II-induced cardiac hypertrophy.

pri-miR-222

Target Gene

Cardiomegaly [ICD-11: BC45]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[308]
Responsed Disease	Cardiomegaly [ICD-11: BC45]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway	hsa04310
In-vitro Model	NRCMs (Primary neonatal rat cardiomyocytes (NRCMs)NRCMs were prepared from the hearts of 2- to 3-day-old SD rats according to the following protocol)
In-vivo Model	The pump was prefilled with Ang-II or saline and then incubated in sterile saline at 37 ℃ for 48 h. After the mice were anesthetized with 3.0% isoflurane mixed with oxygen, an incision was made on the back skin of the mice, and the pump was implanted into the subcutaneous area, followed by suturing the incision. After the operation, the mice were given buprenorphine (0.1 mg/kg) to reach analgesia. Finally, the regaining consciousness mice were returned to cages and fed until the end of the experiment.
Response Summary	METTL3 positively modulates the pri-miR221/pri-miR-222 maturation process in an m6A-dependent manner and subsequently activates Wnt/Beta-catenin signaling by inhibiting DKK2, thus promoting Ang-II-induced cardiac hypertrophy.

pri-miR-27

Target Gene

Multiple myeloma [ICD-11: 2A83]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[228]
Responsed Disease	Multiple myeloma [ICD-11: 2A83.1]
Target Regulation	Down regulation
Cell Process	Cell apoptosis
In-vitro Model	U266 (Human multiple myeloma cells)
	RPMI-8226	Plasma cell myeloma	Homo sapiens	CVCL_0014
	NCI-H929	Plasma cell myeloma	Homo sapiens	CVCL_1600
	MM1.S	Plasma cell myeloma	Homo sapiens	CVCL_8792
In-vivo Model	BALB/C nude mice (5 weeks old, weighing 18-22 g) were fed in specific pathogen-free facilities and subcutaneously inoculated with U266 cells (1 × 10⁶). The mice were randomly divided into 3 groups with 6 mice per group, when the tumor was measurable. Then, miR-27a-3p mimic or sh-METTL3 was injected intratumorally at an interval of 4 days a total of 4 times. Tumor volume was measured using a digital caliper every week and calculated using the formula V = 1/2 (width2 × length).
Response Summary	METTL3 affected the growth, apoptosis, and stemness of MM cells through accelerating the stability of YY1 mRNA and the maturation of pri-miR-27 in vitro and in vivo.

Protein E6 (E6)

Target Gene

Malignant neoplasms of tonsil [ICD-11: 2B69]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[309]
Responsed Disease	Malignant neoplasms of tonsil [ICD-11: 2B69]
Target Regulation	Up regulation
In-vitro Model	WSU-HN26	Squamous cell carcinoma of the oral cavity	Homo sapiens	CVCL_5523
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	C33A2 (The C33A2 cell line originates from C33A and has the subgenomic HPV16 plasmid pBELsLuc stably integrated into the genome)
Response Summary	Overexpression of the ALKBH5 promoted production of intron retention on the human papillomavirus type 16 (HPV16) E6 mRNAs thereby promoting Protein E6 (E6) mRNA production.METLL3 induced production of intron-containing HPV16 E1 mRNAs over spliced E2 mRNAs and altered HPV16 L1 mRNA splicing in a manner opposite to ALKBH5. Overexpression of YTHDC1, enhanced retention of the E6-encoding intron and promoted E6 mRNA production. HPV16 mRNAs are m6A-methylated in tonsillar cancer cells.

Unspecific Target Gene

Viral infections [ICD-11: 1D9Y]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[311]
Responsed Disease	Viral infections [ICD-11: 1D9Y]
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	m6A is the most abundant internal modification described in eukaryotic mRNA and several viral RNA including human respiratory syncytial virus (HRSV) infection. METTL3/METTL14 m6A writer complex plays a negative role in HRSV infections protein synthesis and viral titers, while m6A erasers FTO and ALKBH5 had the opposite effect.

Brain cancer [ICD-11: 2A00]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[312]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Responsed Drug	Temozolomide		Approved	Drug Info
Pathway Response	RNA degradation			hsa03018
Cell Process	mRNA decay
In-vitro Model	U251 (Fibroblasts or fibroblast like cells)
	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
In-vivo Model	Used to inject 10 uL of the U87 MG-TMZ_R-luc cell suspension in the striatum at a depth of 3 mm from the dural surface. One week after the injection of the tumor cells, 40 mg/kg/day of TMZ in saline was administered for over 2 weeks by intraperitoneal injection.
Response Summary	Uncover the fundamental mechanisms underlying the interplay of m6 A RNA modification and histone modification in Temozolomide resistance and emphasize the therapeutic potential of targeting the SOX4/EZH2/METTL3 axis in the treatment of TMZ-resistant glioblastoma.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[313]
Responsed Disease	Glioma [ICD-11: 2A00.0]
Cell Process	RNA editing
In-vitro Model	GSC	Glioma	Epinephelus akaara	CVCL_M752
	MGG8 (The primary tumor)
Response Summary	METTL3 plays a vital role in many steps of RNA processing and orchestrates successful execution of oncogenic pathways in Glioma.

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[315]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
In-vitro Model	EoL-1	Chronic eosinophilic leukemia	Homo sapiens	CVCL_0258
	HL-60	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	Kasumi-1	Myeloid leukemia with maturation	Homo sapiens	CVCL_0589
	MOLM-13	Adult acute myeloid leukemia	Homo sapiens	CVCL_2119
	NOMO-1	Adult acute monocytic leukemia	Homo sapiens	CVCL_1609
	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
In-vivo Model	6- to 10-week-old female Rosa26Cas9/+ mice were treated daily for two weeks with either vehicle or 50 mg kg^-1 STM2457 (STORM). Four weeks after treatment, bone marrow cells from these mice were freshly dissected (as mentioned above) and blocked with anti-mouse CD16/32 (BD Pharmigen, cat. no. 553142) and 10% mouse serum (Sigma).
Response Summary	inhibition of METTL3 by STM2457 targets key stem cell populations of acute myeloid leukaemia and reverses the AML phenotype, preventing or slowing the development of AML in re-transplantation experiments.

Head and neck squamous carcinoma [ICD-11: 2B6E]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[316]
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
In-vitro Model	HOK	Normal	Hexagrammos otakii	CVCL_YE19
	HN-6	Tongue squamous cell carcinoma	Homo sapiens	CVCL_8129
	HN-5	Squamous cell carcinoma of the oral cavity	Homo sapiens	CVCL_8128
	HN-15	Squamous cell carcinoma of the oral cavity	Homo sapiens	CVCL_W297
Response Summary	METTL3 and METTL14 are overexpressed in OSCC tissues and in the HN6 OSCC cell line that promotes cell proliferation. Overexpressed METTL3 or METTL14 is found to be an independent prognostic factor for short overall survival in patients with OSCC.

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[317]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
In-vitro Model	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
Response Summary	The results revealed a negative functional regulation of the LINC01559/miR-106b-5p/PTEN axis in CRC progression and explored a new mechanism of METTL3-mediated m6A modification on LINC01559.

Pancreatic cancer [ICD-11: 2C10]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[318]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Responsed Drug	Gemcitabine		Approved	Drug Info
Pathway Response	Adipocytokine signaling pathway			hsa04920

Cell Process	Epithelial-mesenchymal transition
In-vitro Model	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	HDE-CT cell line (A normal human pancreatic cell line)
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
Response Summary	Lasso regression identified a six-m6A-regulator-signature prognostic model (KIAA1429, HNRNPC, METTL3, YTHDF1, IGF2BP2, and IGF2BP3). Gene set enrichment analysis revealed m6A regulators (KIAA1429, HNRNPC, and IGF2BP2) were related to multiple biological behaviors in pancreatic cancer, including adipocytokine signaling, the well vs. poorly differentiated tumor pathway, tumor metastasis pathway, epithelial mesenchymal transition pathway, gemcitabine resistance pathway, and stemness pathway.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[319]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Cell Process	Mitogen-activated protein kinase cascades
	Ubiquitin-dependent process
	RNA splicing
In-vitro Model	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
Response Summary	METTL3 was associated with mitogen-activated protein kinase cascades, ubiquitin-dependent process and RNA splicing and regulation of cellular process, suggesting functional roles and targets of METTL3. METTL3 is a potent target for enhancing therapeutic efficacy in patients with pancreatic cancer.

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[321]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Response Summary	METTL3 and YTHDF1 expression were found to be correlated with an increased risk and were included in an m6A-related gene signature for predicting prognosis of hepatocellular carcinoma.

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[324]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Cell Process	RNA stability
	RNA degradation (hsa03018)
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
Response Summary	MIR33A can attenuate NSCLC cells proliferation via targeting to the 3'UTR of METTL3 mRNA.

Melanoma [ICD-11: 2C30]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[325]
Responsed Disease	Melanoma [ICD-11: 2C30]
Pathway Response	PI3K-Akt signaling pathway	hsa04151
	Cell cycle	hsa04110
Cell Process	Cell cycle
	Cell apoptosis
	Cell colony formation
	Cell migration
	Cell invasion
Response Summary	hsa-miR-302a-3p targets METTL3 and plays tumour suppressive roles in the proliferation, apoptosis, invasion, and migration of melanoma cells.

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[326]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Cell Process	Cell apoptosis
In-vitro Model	CRL-11731D cell line (Human ovarian cancer cell)
	TOV-112D	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_3612
Response Summary	METTL3 can regulate m6A methylation independently of METTL14 and WTAP in endometrioid epithelial ovarian cancer.

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[327]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
Response Summary	CD33+ MDSC expansion is linked to high levels of METTL3 and that METTL3 and CD33+ MDSCs are independent prognostic factors in CC.

Renal cell carcinoma [ICD-11: 2C90]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[328]
Responsed Disease	Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Pathway Response	mTOR signaling pathway	hsa04150
Cell Process	Adipogenesis
Response Summary	It is plausible that VHL-HIF-METTL3/14 pathways are involved in the m6A regulation in clear cell renal cell carcinoma cells, and PI3K-mTOR as well as p53 signaling pathways are possible downstream targets of m6A in ccRCC.

Hematological disorders [ICD-11: 3C0Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[330]
Responsed Disease	Hematological disorders [ICD-11: 3C0Z]
Response Summary	This reviewed summarize and discuss recent findings regarding the biological functions and underlying mechanisms of m6A modification(i.e., the METTL3/METTL14/WTAP complex and other cofactor proteins) and the associated machinery in normal hematopoiesis and the initiation, progression, and drug response of acute myeloid leukemia (AML), a major subtype of leukemia usually associated with unfavorable prognosis.

Obesity [ICD-11: 5B81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[331]
Responsed Disease	Obesity [ICD-11: 5B81]
Cell Process	Adipogenesis
In-vitro Model	3T3F442A	Normal	Mus musculus	CVCL_0122
	3T3-L1	Normal	Mus musculus	CVCL_0123
	COS (From the African green monkey cell line (CV-1).)
	MEF (Mouse embryonic fibroblasts)
In-vivo Model	Mice were anesthetized after 24 h of fasting, and 5 U of human insulin (Humalin R; Eli Lilly) was injected into the inferior vena cava. After 5 min, the liver and hind limb muscles were dissected and immediately frozen in liquid nitrogen.
Response Summary	WTAP, coupled with METTL3 and METTL14, is increased and distributed in nucleus by the induction of adipogenesis dependently on RNA in vitro Knockdown of each of these three proteins leads to cell cycle arrest and impaired adipogenesis associated with suppression of cyclin A2 upregulation during MCE, whose knockdown also impairs adipogenesis.

Alzheimer disease [ICD-11: 8A20]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[332]
Responsed Disease	Alzheimer disease [ICD-11: 8A20]
Cell Process	Synaptic or neuron development and growth
Response Summary	The alterations of m6A RNA methylation in alzheimer's disease and in C57BL/6 mice were investigated using high-throughput sequencing. The expression of the m6A methyltransferase METTL3 was elevated and that of the m6A demethylase FTO was decreased in AD mice.

Muscular dystrophies [ICD-11: 8C70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[335]
Responsed Disease	Muscular dystrophies [ICD-11: 8C70]
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vitro Model	C2C12	Normal	Mus musculus	CVCL_0188
In-vivo Model	For mouse muscle injury and regeneration experiment, tibialis anterior (TA) muscles of six-week-old male mice were injected with 25 uL of 10 uM cardiotoxin (CTX, Merck millipore, 217 503), then the C2C12 cells, which stably overexpressed METTL3 or GFP control, were injected to the injury site of mice on the following day. The regenerated muscles were collected at day 7 post-injection, frozen in liquid nitrogen for RNA and protein extraction.
Response Summary	muscle specific miRNAs are essential for skeletal muscle differentiation. METTL3 regulated the expressions of muscle specific miRNAs by multiple mechanisms.

Cortical development [ICD-11: 8E4Y]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[336]
Responsed Disease	Cortical development [ICD-11: 8E4Y]
In-vivo Model	Homologous recombination was used, cas9 mRNA, gRNA, and donor vector were microinjected into the fertilized eggs of C57BL/6J mice to obtain F0 generation mice.
Response Summary	Knockout of Mettl3 leads to a more severe disruption of translational regulation of mRNAs than deletion of Fto and results in altered translation of crucial genes in cortical radial glial cells and intermediate progenitors. Uncover a profound role of Mettl3 in regulating translation of major mRNAs that control proper cortical development.

Disorders of the retina [ICD-11: 9B70-9C0Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[337]
Responsed Disease	Disorders of the retina [ICD-11: 9B70-9C0Z]
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	ARPE-19	Normal	Homo sapiens	CVCL_0145
In-vivo Model	The vitreous cavity of the right eye of each rat was injected either with ARPE-19 cells (1 × 10⁵ per uL in PBS [pH 7.4]) overexpressing METTL3 or control vector cells or with an equal volume of PBS (pH 7.4).
Response Summary	METTL3 is involved in the PVR process, and METTL3 overexpression inhibits the EMT of ARPE-19 cells in vitro and suppresses the PVR process in vivo.

Cardiomegaly [ICD-11: BC45]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[338]
Responsed Disease	Cardiomegaly [ICD-11: BC45]
Cell Process	Heart failure
In-vitro Model	Neonatal rat ventricular cardiomyocytes (Primary myocyte cells)
In-vivo Model	Mettl3 fl/fl mice were crossed with mice expressing cre recombinase under the control of the cardiac-specific Myh7 promoter (Beta-myosin heavy chain [Beta-MHC]) to obtain heart-restricted deletion of Mettl3 (METTL3-cKO; cKO).
Response Summary	Inhibition of METTL3 completely abrogated the ability of cardiomyocytes to undergo hypertrophy when stimulated to grow, whereas increased expression of the m6A RNA methylase METTL3 was sufficient to promote cardiomyocyte hypertrophy both in vitro and in vivo.

Liver disease [ICD-11: DB9Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[339]
Responsed Disease	Liver disease [ICD-11: DB9Z]
Pathway Response	PPAR signaling pathway	hsa03320
Cell Process	Fatty degeneration
In-vivo Model	A total of 24 male mice were randomly allocated to LFD (low-fat diet), LFDR (low-fat diet + resveratrol), HFD (high-fat diet), and HFDR (high-fat diet + resveratrol) groups for 12 weeks (n = 6/group).
Response Summary	The beneficial effect of resveratrol on lipid metabolism disorder under HFD is due to a decrease of m6A RNA methylation and an increase of PPARalpha mRNA, providing mechanistic insights into the function of resveratrol in alleviating the disturbance of lipid metabolism in mice. The resveratrol in HFD increased the transcript levels of methyltransferase like 3 (METTL3), alkB homolog 5 (ALKBH5), fat mass and obesity associated protein (FTO), and YTH domain family 2 (YTHDF2), whereas it decreased the level of YTH domain family 3 (YTHDF3) and m6A abundance in mice liver.

Rheumatoid arthritis [ICD-11: FA20]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[340]
Responsed Disease	Rheumatoid arthritis [ICD-11: FA20]
Target Regulation	Up regulation
Pathway Response	TNF signaling pathway			hsa04668
Cell Process	Inflammation in macrophages
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
Response Summary	LPS could enhance the expression and biological activity of METTL3 in macrophages, while overexpression of METTL3 significantly attenuated the inflammatory response induced by LPS in macrophages.This study firstly demonstrates the critical role of METTL3 in RA, which provides novel insights into recognizing the pathogenesis of Rheumatoid Arthritis(RA) and a promising biomarker for RA.

Low bone mass disorder [ICD-11: FB83]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[341]
Responsed Disease	Osteoporosis [ICD-11: FB83.1]
Pathway Response	Wnt signaling pathway	hsa04310
Cell Process	Bone formation
In-vivo Model	OP rats were fixed prone, the skin was prepared and the skull was disinfected, resulting in a full-thickness defect of 8mm. BCP incubated with OP-BMSCs was implanted in the skull defect area. After 8 weeks, skull specimens were taken after the rats were euthanized.
Response Summary	Overexpression of Mettl3 could partially rescue the decreased bone formation ability of OP-BMSCs by the canonical Wnt signalling pathway. Therefore, Mettl3 can be a key targeted gene for bone generation and therapy of bone defects in OP patients.

Male infertility [ICD-11: GB04]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[342]
Responsed Disease	Male infertility [ICD-11: GB04]
Responsed Drug	Ethyl ester form of meclofenamic acid		Approved	Drug Info
Cell Process	Cell cycle
	Cell proliferation
In-vitro Model	GC-1 spg	Normal	Mus musculus	CVCL_8872
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Mouse GC-1 spg cells were treated with the ester form of meclofenamic acid (MA2) to inhibit the demethylase activity of FTO.
Response Summary	METTL3, METTL14, ALKBH5 and YTHDC2 are involved in the regulation of spermatogenesis and oogenesis. MA2 affected CDKs expression through the m6A-dependent mRNA degradation pathway, and thus repressed spermatogonial proliferation. Additionally, mutation of the predicted m6A sites in the Cdk2-3'UTR could mitigated the degradation of CDK2 mRNA after MA2 treatment.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[343]
Responsed Disease	Male infertility [ICD-11: GB04]
Cell Process	SSC proliferation/differentiation
In-vitro Model	Spermatogenic cells (Prepared from undifferentiated mouse spermatogonial cells)
In-vivo Model	All mice described above were maintained on the C57BL/6J (B6) background. Mettl3- and Mettl14-floxed mice (Mettl3^flox/flox and Mettl14^flox/flox) were then bred with germ cell-specific expressed Cre mice including Vasa-Cre mouse line (Jackson Laboratory, Bar Harbor, Maine, USA) and Stra8-GFPCre mouse line for excising the loxP-flanked exon 4 and exon 2 to generate germ cell-specific Mettl3 and Mettl14KO mice, respectively. Germ cell-specific Mettl3 and Mettl14 double KO mice were obtained by crossing Mettl3^flox/floxMettl14^flox/flox with Mettl3^flox/+Mettl14^flox/+ or Mettl3^flox/+Mettl14^flox/flox carried germ cell-specific expressed Cre mice.
Response Summary	Combined deletion of Mettl3 and Mettl14 in advanced germ cells with Stra8-GFPCre disrupts spermiogenesis, whereas mice with single deletion of either Mettl3 or Mettl14 in advanced germ cells show normal spermatogenesis.

CNS anomalies syndrome [ICD-11: LD20]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[344]
Responsed Disease	Pontocerebellar hypoplasia [ICD-11: LD20.01]
Cell Process	Extended RNA half-lives and aberrant splicing
	Cell apoptosis
In-vitro Model	CGC (Conjunctival goblet cells)
	Neural stem cell (NSC) lines (A group of ectodermal progenitor cells)
In-vivo Model	All pups were genotyped and two Mettl3^flox/+ founder mice were obtained.
Response Summary	METTL3 depletion-induced loss of m6A modification causes extended RNA half-lives and aberrant splicing events, consequently leading to dysregulation of transcriptome-wide gene expression and premature CGC death.Mettl3 in mouse nervous system causes severe developmental defects in the brain.

Exposure to radiation [ICD-11: PH73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[345]
Responsed Disease	Exposure to radiation [ICD-11: PH73]
In-vitro Model	MRC-5	Normal	Homo sapiens	CVCL_0440
Response Summary	m6A RNA methylation has been defined and appears to affect DNA repair by modulation of translation.

COVID-19 [ICD-11: RA01]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[346]
Responsed Disease	COVID-19 [ICD-11: RA01]
In-vitro Model	Vero E6 (African green monkey kidney cell Vero E6 cells (ATCC CLR-1586))
	MRC-5	Normal	Homo sapiens	CVCL_0440
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Response Summary	replication of SARS-CoV-2, the agent responsible for the COVID-19 pandemic, and a seasonal human Bete-coronavirus HCoV-OC43, can be suppressed by depletion of METTL3 or cytoplasmic m6A reader proteins YTHDF1 and YTHDF3 and by a highly specific small molecule METTL3 inhibitor.

ATP-binding cassette sub-family C member 9 (ABCC9)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	ARPE-19 cell line	Homo sapiens
Treatment: shMETTL3 ARPE-19 cells Control: shControl ARPE-19 cells		GSE202017
Regulation		logFC: -1.97E+00 p-value: 5.10E-08
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 6.69E+00	GSE60213

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[14]
Responsed Disease	Nasopharyngeal carcinoma		ICD-11: 2B6B	Disease Info
Target Regulation	Down regulation
Pathway Response	ABC transporters			hsa02010
	Wnt signaling pathway			hsa04310
	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Ubiquitination degradation
In-vitro Model	CNE-1	Normal	Homo sapiens	CVCL_6888
	CNE-2	Nasopharyngeal carcinoma	Homo sapiens	CVCL_6889
In-vivo Model	A total of 2 × 10⁶ cells was mixed with 0.2 ml PBS (pH 7.4) and 30% (v/v) Matrigel matrix (BD Biosciences).
Response Summary	TRIM11 regulates nasopharyngeal carcinoma drug resistance by positively modulating the Daple/beta-catenin/ATP-binding cassette sub-family C member 9 (ABCC9) signaling pathway. TRIM11 enhanced the multidrug resistance in NPC by inhibiting apoptosis in vitro and promoting cisplatin (DDP) resistance in vivo. METTL3-mediated m6A modification caused the upregulation of TRIM11 via IGF2BP2 in NPC drug-resistant cells.

Autophagy protein 5 (ATG5)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	CT26 cell line	Mus musculus
Treatment: METTL3 knockout CT26 cells Control: CT26 cells		GSE142589
Regulation		logFC: -9.09E-01 p-value: 4.91E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 8.30E+00	GSE60213

Sorafenib [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[17]
Responsed Disease	Hepatocellular carcinoma	ICD-11: 2C12.02	Disease Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, Autophagy protein 5 (ATG5), ATG12, and ATG16L1.

Chloroquine [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as Autophagy protein 5 (ATG5), ATG7, LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.

Gefitinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as Autophagy protein 5 (ATG5), ATG7, LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.

Beta-Elemen [Phase 3]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as Autophagy protein 5 (ATG5), ATG7, LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[19]
Responsed Disease	Testicular cancer		ICD-11: 2C80	Disease Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular Processes
	Cellular Transport
	Cellular catabolism
	Cell autophagy
In-vitro Model	Tcam-2/DDP (Cisplatin-resistant TCam-2 cell line)
	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012
Response Summary	m6A methyltransferase METTL3 regulates autophagy and sensitivity to cisplatin by targeting Autophagy protein 5 (ATG5) in seminoma. The use of autophagy inhibitors 3-MA could reverse the protective effect of METTL3 on TCam-2 cells.

3-Methyladenine [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[19]
Responsed Disease	Testicular cancer		ICD-11: 2C80	Disease Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular Processes
	Cellular Transport
	Cellular catabolism
	Cell autophagy
In-vitro Model	Tcam-2/DDP (Cisplatin-resistant TCam-2 cell line)
	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012
Response Summary	m6A methyltransferase METTL3 regulates autophagy and sensitivity to cisplatin by targeting Autophagy protein 5 (ATG5) in seminoma. The use of autophagy inhibitors 3-MA could reverse the protective effect of METTL3 on TCam-2 cells.

Autophagy-related protein 16-1 (ATG16L1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	CT26 cell line	Mus musculus
Treatment: METTL3 knockout CT26 cells Control: CT26 cells		GSE142589
Regulation		logFC: -8.44E-01 p-value: 3.07E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.03E+00	GSE60213

Sorafenib [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[17]
Responsed Disease	Hepatocellular carcinoma	ICD-11: 2C12.02	Disease Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, ATG7, ATG12, and Autophagy-related protein 16-1 (ATG16L1).

Broad substrate specificity ATP-binding cassette transporter ABCG2 (BCRP/ABCG2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -9.03E-01 p-value: 2.29E-02
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 4.88E+00	GSE60213

Doxil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[22]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
Cell Process	Cell growth and death
	Cell apoptosis
In-vitro Model	ADR-resistant MCF-7 (MCF-7/ADR) cells (Human breast cancer doxorubicin-resistant cell line)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
In-vivo Model	Cell suspensions (2 × 10⁶ cells/mL) made with MCF-7/ADR cells stably expressing METTL3 and/or miR-221-3p inhibitor were subcutaneously implanted into each mouse. One week later, xenografted mice were injected with 0.1 mL ADR (25 mg/kg, intraperitoneal injection) twice a week.
Response Summary	METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating pri-microRNA-221-3p maturation in a m6A-dependent manner. METTL3 knockdown was shown to reduce the expression of miR-221-3p by reducing pri-miR-221-3p m6A mRNA methylation, reducing the expression of MDR1 and Broad substrate specificity ATP-binding cassette transporter ABCG2 (BCRP/ABCG2), and inducing apoptosis. Identified the METTL3/miR-221-3p/HIPK2/Che-1 axis as a novel signaling event that will be responsible for resistance of BC cells to ADR.

Cellular tumor antigen p53 (TP53/p53)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HeLa cell line	Homo sapiens
Treatment: METTL3 knockdown HeLa cells Control: HeLa cells		GSE70061
Regulation		logFC: 1.12E+00 p-value: 1.48E-02
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.05E+00	GSE60213

Arsenite [Phase 2]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[27]
Responsed Disease	Solid tumour/cancer		ICD-11: 2A00-2F9Z	Disease Info
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
In-vitro Model	HaCaT	Normal	Homo sapiens	CVCL_0038
Response Summary	METTL3 significantly decreased m6A level, restoring Cellular tumor antigen p53 (TP53/p53) activation and inhibiting cellular transformation phenotypes in the arsenite-transformed cells. m6A downregulated the expression of the positive p53 regulator, PRDM2, through the YTHDF2-promoted decay of PRDM2 mRNAs. m6A upregulated the expression of the negative p53 regulator, YY1 and MDM2 through YTHDF1-stimulated translation of YY1 and MDM2 mRNA. This study further sheds light on the mechanisms of arsenic carcinogenesis via RNA epigenetics.

Apatinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[30]
Responsed Disease	Hepatocellular carcinoma		ICD-11: 2C12.02	Disease Info
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	QGY-7701	Human papillomavirus-related endocervical adenocarcinoma	Homo sapiens	CVCL_6859
	HHL-5	Normal	Homo sapiens	CVCL_S956
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Nude mice (4-6 week-old) were administered sterile water and feed in a specific pathogen-free barrier. Using a 1-mL syringe, 1 × 10⁷ HEPG2 cells were subcutaneously inoculated into the right axilla of nude mice to build the HCC xenograft model. When the tumor volume reached 50 mm3, the nude mice were randomly divided into 1 control (n = 4) and 3 treatment groups (n = 4 each). RG7112, apatinib, and RG7112 + apatinib were administered to the treatment groups and an equal volume of dimethyl sulfoxide to the control group by daily gavage for 14 d. The tumor length (L) and width (W) were measured on alternate days using vernier calipers. The following formula was used to calculate the tumor volume: volume (mm3) = 0.5 × L × W × W. At the end of the experiment, the nude mice were killed by CO2 overdose anesthesia. The tumors were dissected and weighed using a precision balance, and the tumor tissue was stored in liquid nitrogen for further analysis.
Response Summary	Cellular tumor antigen p53 (TP53/p53) n6-methyladenosine (m6A) played a decisive role in regulating Hepatocellular carcinoma(HCC) sensitivity to chemotherapy via the p53 activator RG7112 and the vascular endothelial growth factor receptor inhibitor apatinib. p53 mRNA m6A modification blockage induced by S-adenosyl homocysteine or siRNA-mediated METTL3 inhibition enhanced HCC sensitivity to chemotherapy.

RG7112 [ Phase 1]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[30]
Responsed Disease	Hepatocellular carcinoma		ICD-11: 2C12.02	Disease Info
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell apoptosis
In-vitro Model	QGY-7701	Human papillomavirus-related endocervical adenocarcinoma	Homo sapiens	CVCL_6859
	HHL-5	Normal	Homo sapiens	CVCL_S956
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	Nude mice (4-6 week-old) were administered sterile water and feed in a specific pathogen-free barrier. Using a 1-mL syringe, 1 × 10⁷ HEPG2 cells were subcutaneously inoculated into the right axilla of nude mice to build the HCC xenograft model. When the tumor volume reached 50 mm3, the nude mice were randomly divided into 1 control (n = 4) and 3 treatment groups (n = 4 each). RG7112, apatinib, and RG7112 + apatinib were administered to the treatment groups and an equal volume of dimethyl sulfoxide to the control group by daily gavage for 14 d. The tumor length (L) and width (W) were measured on alternate days using vernier calipers. The following formula was used to calculate the tumor volume: volume (mm3) = 0.5 × L × W × W. At the end of the experiment, the nude mice were killed by CO2 overdose anesthesia. The tumors were dissected and weighed using a precision balance, and the tumor tissue was stored in liquid nitrogen for further analysis.
Response Summary	Cellular tumor antigen p53 (TP53/p53) n6-methyladenosine (m6A) played a decisive role in regulating Hepatocellular carcinoma(HCC) sensitivity to chemotherapy via the p53 activator RG7112 and the vascular endothelial growth factor receptor inhibitor apatinib. p53 mRNA m6A modification blockage induced by S-adenosyl homocysteine or siRNA-mediated METTL3 inhibition enhanced HCC sensitivity to chemotherapy.

Homeodomain-interacting protein kinase 2 (HIPK2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -1.67E+00 p-value: 2.62E-66
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.33E+00	GSE60213

Doxil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[22]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
Cell Process	Cell growth and death
	Cell apoptosis
In-vitro Model	ADR-resistant MCF-7 (MCF-7/ADR) cells (Human breast cancer doxorubicin-resistant cell line)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
In-vivo Model	Cell suspensions (2 × 10⁶ cells/mL) made with MCF-7/ADR cells stably expressing METTL3 and/or miR-221-3p inhibitor were subcutaneously implanted into each mouse. One week later, xenografted mice were injected with 0.1 mL ADR (25 mg/kg, intraperitoneal injection) twice a week.
Response Summary	METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating pri-microRNA-221-3p maturation in a m6A-dependent manner. METTL3 knockdown was shown to reduce the expression of miR-221-3p by reducing pri-miR-221-3p m6A mRNA methylation, reducing the expression of MDR1 and BCRP, and inducing apoptosis. Identified the METTL3/miR-221-3p/Homeodomain-interacting protein kinase 2 (HIPK2)/Che-1 axis as a novel signaling event that will be responsible for resistance of BC cells to ADR.

Kelch-like ECH-associated protein 1 (KEAP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HeLa cell line	Homo sapiens
Treatment: METTL3 knockdown HeLa cells Control: HeLa cells		GSE70061
Regulation		logFC: -1.79E+00 p-value: 1.23E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.17E+00	GSE60213

Colistin [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[65]
Responsed Disease	Diseases of the urinary system	ICD-11: GC2Z	Disease Info
Target Regulation	Down regulation
Cell Process	Oxidative stress
	Cell apoptosis
In-vivo Model	The 60 female Kunming mice were divided into two groups (n = 30): control group (injection of physiological saline through the caudal vein) and colistin group (injection of 15 mg/kg colistin, twice a day, with an eight-hour interval).
Response Summary	m6A methylation was involved in oxidative stress-mediated apoptosis in the mechanism of colistin nephrotoxicity. METTL3-mediated M6A methylation modification is involved in colistin-induced nephrotoxicity through apoptosis mediated by Kelch-like ECH-associated protein 1 (KEAP1)/Nrf2 signaling pathway.

Methylated-DNA--protein-cysteine methyltransferase (MGMT)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -1.79E+00 p-value: 2.16E-20
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 5.15E+00	GSE60213

Temozolomide [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[69]
Responsed Disease	Glioblastoma		ICD-11: 2A00.00	Disease Info
Target Regulation	Down regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	DNA repair
In-vitro Model	U251 (Fibroblasts or fibroblast like cells)
	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
In-vivo Model	Subcutaneously injected shMETTL3 or shNC-expressing U87-MG-TMZ cells into BALB/c NOD mice. After confirmation of GBM implantation, mice were treated with TMZ (66 mg/kg/d, 5 d per week, for 3 cycles).
Response Summary	Two critical DNA repair genes (Methylated-DNA--protein-cysteine methyltransferase (MGMT) and APNG) were m6A-modified by METTL3, whereas inhibited by METTL3 silencing or DAA-mediated total methylation inhibition, which is crucial for METTL3-improved temozolomide resistance in glioblastoma cells.

Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B/LC3B-II)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 6.38E-01 p-value: 4.93E-09
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.34E+00	GSE60213

Chloroquine [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, ATG7, LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B/LC3B-II). beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.

Gefitinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, ATG7, LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B/LC3B-II). beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.

Beta-Elemen [Phase 3]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, ATG7, LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B/LC3B-II). beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.

Neurocalcin-delta (NCALD)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LNCaP cell line	Homo sapiens
Treatment: shMETTL3 LNCaP cells Control: shControl LNCaP cells		GSE147884
Regulation		logFC: 1.15E+00 p-value: 3.16E-04
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 8.03E+00	GSE60213

Fluorouracil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[88]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Down regulation
In-vitro Model	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vivo Model	A tumor-bearing model was established by subcutaneously injecting 100 ul HT29 cells (5×10⁶) followed by an intravenous injection of CAFs-derived exosomes (50 ug/mouse every three days) into the tail vein of the mice. An intraperitoneal injection of 5-FU (50 mg/kg, every week) was administered on day 12.
Response Summary	METTL3?dependent m6A methylation was upregulated in CRC to promote the processing of miR?181d?5p by DGCR8. This led to increased miR?181d?5p expression, which inhibited the 5?FU sensitivity of CRC cells by targeting Neurocalcin-delta (NCALD).

Pro-epidermal growth factor (EGF)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HeLa cell line	Homo sapiens
Treatment: METTL3 knockdown HeLa cells Control: HeLa cells		GSE70061
Regulation		logFC: 2.08E+00 p-value: 3.08E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 7.98E+00	GSE60213

Doxil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[98]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
Pathway Response	Homologous recombination			hsa03440
Cell Process	Homologous recombination repair
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
In-vivo Model	Cells were trypsinized and resuspended in DMEM at a consistence of 1 × 10⁷ cells/ml. A total of 1 × 106 cells were injected into flank of mice. 27 days after injection, tumors were removed for paraffin-embedded sections.
Response Summary	Knockdown of METTL3 sensitized these breast cancer cells to Adriamycin (ADR; also named as doxorubicin) treatment and increased accumulation of DNA damage. Mechanically, we demonstrated that inhibition of METTL3 impaired HR efficiency and increased ADR-induced DNA damage by regulating m6A modification of Pro-epidermal growth factor (EGF)/RAD51 axis. METTL3 promoted EGF expression through m6A modification, which further upregulated RAD51 expression, resulting in enhanced HR activity.

Sequestosome-1 (SQSTM1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HUVEC cell line	Homo sapiens
Treatment: shMETTL3 HUVEC cells Control: shScramble HUVEC cells		GSE157544
Regulation		logFC: -6.28E-01 p-value: 1.94E-05
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.03E+00	GSE60213

Chloroquine [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, ATG7, LC3B, and Sequestosome-1 (SQSTM1). beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.

Gefitinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, ATG7, LC3B, and Sequestosome-1 (SQSTM1). beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.

Beta-Elemen [Phase 3]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, ATG7, LC3B, and Sequestosome-1 (SQSTM1). beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.

TNF receptor-associated factor 5 (TRAF5)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -7.59E-01 p-value: 1.50E-05
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.24E+00	GSE60213

Oxaliplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[113]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Down regulation
In-vitro Model	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vivo Model	HCT-116 cells (3 × 10⁵ cells in 200 uL of saline) were subcutaneously injected into the nude mice to establish xenograft tumors. After 10 days, 10 mg/kg OX or saline was intraperitoneally injected (n = 5 for each group). Si-METTL3 or si-TRAF5 (10 nmol/20 g body weight) was injected twice intratumorally before the start of OX treatment. The mice were examined every 2 days and sacrificed 4 weeks after the OX treatment.
Response Summary	2-polarized tumor-associated macrophages enabled the oxaliplatin resistance via the elevation of METTL3-mediated m6A modification in Colorectal Cancer cells. Furthermore, they found that TNF receptor-associated factor 5 (TRAF5) contributes to the METTL3-triggered OX resistance in CRC cells.

Transcription factor AP-2 gamma (TFAP2C)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Embryonic stem cells	Mus musculus
Treatment: METTL3-/- mESCs Control: Wild type ESCs		GSE147849
Regulation		logFC: 1.20E+00 p-value: 4.47E-08
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 2.28E+00	GSE60213

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[115]
Responsed Disease	Testicular cancer		ICD-11: 2C80	Disease Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	DNA repair
In-vitro Model	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012
In-vivo Model	Male mice were subcutaneously injected with tumour cells near the limbs to establish xenografts (1 × 10⁶/mouse, 0.2 mL for each injection site; METTL3-overexpressing TCam-2/CDDP cells were inoculated once at the initial time and IGF2BP1-inhibited TCam-2/CDDP cells were inoculated every 3 days).
Response Summary	METTL3 potentiates resistance to cisplatin through m6A modification of Transcription factor AP-2 gamma (TFAP2C) in seminoma. Enhanced stability of TFAP2C mRNA promoted seminoma cell survival under cisplatin treatment burden probably through up-regulation of DNA repair-related genes. IGF2BP1 binds to TFAP2C and enhances TFAP2C mRNA stability.

Transcription factor E2F1 (E2F1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: 8.59E-01 p-value: 2.73E-57
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.01E+00	GSE60213

Doxil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[116]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
In-vitro Model	MCF7-DoxR (Adriamycin-resistant cell line MCF7-DoxR)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
In-vivo Model	Once the tumor volume increased to about 1 cm3, six groups of MCF7 bearing mice (n = 10 in each group) were injected with PBS (0.1 ml, caudal vein) and adriamycin (0.1 ml, 10 mg/kg), respectively. When the tumor reached 1.5 cm in any direction (defined as event-free survival analysis), 10 mice in each group were selected to measure the tumor size and weight on the 12th day after adriamycin injection.
Response Summary	METTL3 can regulate the expression of MALAT1 through m6A, mediate the Transcription factor E2F1 (E2F1)/AGR2 axis, and promote the adriamycin resistance of breast cancer.

Transcriptional coactivator YAP1 (YAP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LNCaP cell line	Homo sapiens
Treatment: shMETTL3 LNCaP cells Control: shControl LNCaP cells		GSE147884
Regulation		logFC: 6.80E-01 p-value: 6.99E-58
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.22E+00	GSE60213

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[126]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 10⁶ lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-Transcriptional coactivator YAP1 (YAP1) axis to induce Non-small cell lung cancer drug resistance and metastasis.

Translocation protein SEC62 (SEC62)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	CT26 cell line	Mus musculus
Treatment: METTL3 knockout CT26 cells Control: CT26 cells		GSE142589
Regulation		logFC: -8.61E-01 p-value: 1.21E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.99E+00	GSE60213

Fluorouracil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[128]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Protein degradation
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
In-vitro Model	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
In-vivo Model	DLD-1 cells were subcutaneously implanted into 4-6 weeks old female nude mice. When tumors reached a size of about 50 mm³, the nude mice were randomly divided into 6 groups.
Response Summary	Translocation protein SEC62 (SEC62) upregulated by the METTL3-mediated m6A modification promotes the stemness and chemoresistance of colorectal cancer by binding to beta-catenin and enhancing Wnt signalling. Depletion of Sec62 sensitized the CRC cells to 5-Fu or oxaliplatin treatment.

Oxaliplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[128]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Protein degradation
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
In-vitro Model	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
In-vivo Model	DLD-1 cells were subcutaneously implanted into 4-6 weeks old female nude mice. When tumors reached a size of about 50 mm³, the nude mice were randomly divided into 6 groups.
Response Summary	Translocation protein SEC62 (SEC62) upregulated by the METTL3-mediated m6A modification promotes the stemness and chemoresistance of colorectal cancer by binding to beta-catenin and enhancing Wnt signalling. Depletion of Sec62 sensitized the CRC cells to 5-Fu or oxaliplatin treatment.

Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 6.17E-01 p-value: 3.67E-05
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 4.77E+00	GSE60213

Sorafenib [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[17]
Responsed Disease	Hepatocellular carcinoma	ICD-11: 2C12.02	Disease Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), ATG12, and ATG16L1.

Chloroquine [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.

Gefitinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.

Beta-Elemen [Phase 3]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[18]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagic lysosome acidification
In-vitro Model	Gefitinib-resistant cell line HCC827GR (Gefitinib-resistant HCC827 cell line)
	Gefitinib-resistant cell line PC9GR (Gefitinib-resistant PC9 cell line)
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vivo Model	NSCLC gefitinib-resistant cells (5 × 10⁶ cells in 100 uL PBS) were injected subcutaneously into the lateral surface of the left abdomen of 6-week-old female BALB/c nude mice (at least five mice per group to ensure accuracy).
Response Summary	METTL3 could positively regulate the autophagy by targeting the autophagy-related genes such as ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), LC3B, and SQSTM1. beta-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. beta-elemene could reverse gefitinib resistance in non-small cell lung cancer cells by inhibiting cell autophagy process in a manner of chloroquine. METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by beta-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.

Ubiquitin-like protein ATG12 (ATG12)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Mouse testis	Mus musculus
Treatment: Mettl3 knockout mouse testis Control: Mouse testis		GSE99771
Regulation		logFC: -2.94E+00 p-value: 6.14E-05
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.85E+00	GSE60213

Sorafenib [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[17]
Responsed Disease	Hepatocellular carcinoma	ICD-11: 2C12.02	Disease Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, ATG7, Ubiquitin-like protein ATG12 (ATG12), and ATG16L1.

LBX2 antisense RNA 1 (LBX2-AS1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -8.54E-01 p-value: 2.13E-07
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 6.38E+00	GSE60213

Fluorouracil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[138]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Up regulation
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vitro Model	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	The increased LBX2 antisense RNA 1 (LBX2-AS1) in CRC was mediated by METTL3-dependent m6A methylation. LBX2-AS1 serves as a therapeutic target and predictor of 5-FU benefit in colorectal cancer patients.

Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	DKO-1 cell line	Homo sapiens
Treatment: METTL3 knockdown DKO-1 cell Control: DKO-1 cell		GSE182382
Regulation		logFC: 8.20E-01 p-value: 5.93E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.28E+00	GSE60213

Cisplatin [Approved]

In total 2 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[126]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 10⁶ lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.
Experiment 2 Reporting the m6A-centered Drug Response of This Target Gene				[144]
Responsed Disease	Thymic epithelial tumors		ICD-11: 2C27.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Cellular senescence			hsa04218
Cell Process	Cell viability and proliferation
In-vitro Model	T1889	Thymic undifferentiated carcinoma	Homo sapiens	CVCL_D024
Response Summary	This study highlighted METTL3 as a tumor promoter in Thymic tumors and c-MYC as a promising target to be exploited for the treatment of TET. High expression of c-MYC protein is enabled by lncRNA Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), which is methylated and delocalized by METTL3. Silencing of METTL3 combined with cisplatin or c-MYC inhibitor induces cell death in TET cells. Blocking of c-MYC by using JQ1 inhibitor cooperates with METTL3 depletion in the inhibition of proliferation and induction of cell death.

JQ-1 [Phase 1]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[144]
Responsed Disease	Thymic epithelial tumors		ICD-11: 2C27.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Cellular senescence			hsa04218
Cell Process	Cell viability and proliferation
In-vitro Model	T1889	Thymic undifferentiated carcinoma	Homo sapiens	CVCL_D024
Response Summary	This study highlighted METTL3 as a tumor promoter in Thymic tumors and c-MYC as a promising target to be exploited for the treatment of TET. High expression of c-MYC protein is enabled by lncRNA Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), which is methylated and delocalized by METTL3. Silencing of METTL3 combined with cisplatin or c-MYC inhibitor induces cell death in TET cells. Blocking of c-MYC by using JQ1 inhibitor cooperates with METTL3 depletion in the inhibition of proliferation and induction of cell death.

Doxil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[116]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
In-vitro Model	MCF7-DoxR (Adriamycin-resistant cell line MCF7-DoxR)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
In-vivo Model	Once the tumor volume increased to about 1 cm3, six groups of MCF7 bearing mice (n = 10 in each group) were injected with PBS (0.1 ml, caudal vein) and adriamycin (0.1 ml, 10 mg/kg), respectively. When the tumor reached 1.5 cm in any direction (defined as event-free survival analysis), 10 mice in each group were selected to measure the tumor size and weight on the 12th day after adriamycin injection.
Response Summary	METTL3 can regulate the expression of Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) through m6A, mediate the E2F1/AGR2 axis, and promote the adriamycin resistance of breast cancer.

Artenimol [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[145]
Responsed Disease	Chronic kidney disease		ICD-11: GB61	Disease Info
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	HK-2 [Human kidney]	Normal	Homo sapiens	CVCL_0302
In-vitro Model	HK2	Normal	Acipenser baerii	CVCL_YE28
In-vivo Model	For the unilateral ureteral obstruction (UUO) model, male C57BL/6J mice at 8 weeks of age (20-22 g body weight) were first anaesthetized with pentobarbital sodium (50 mg/kg) via intraperitoneal injection. Then, the left ureter was ligated using 3-0 silk and a left lateral incision.
Response Summary	Renal fibrosis is a key factor in chronic kidney disease (CKD). Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)/miR-145/FAK pathway was involved in the effect of dihydroartemisinin (DHA) on TGF-beta1-induced renal fibrosis in vitro and in vivo.

Adenylate kinase 4, mitochondrial (AK4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -5.87E-01 p-value: 2.40E-51
More Results	Click to View More RNA-seq Results

Tamoxifen [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[152]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
Cell Process	Mitochondrial apoptosis
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
In-vitro Model	MCF7-TamR	Invasive breast carcinoma	Homo sapiens	CVCL_EG55
Response Summary	Adenylate kinase 4 modulates the resistance of breast cancer cells to tamoxifen through an m6A-based epitranscriptomic mechanism. Genetic depletion of METTL3 in TamR MCF-7 cells led to a diminished Adenylate kinase 4, mitochondrial (AK4) protein level and attenuated resistance to tamoxifen.

Anterior gradient protein 2 homolog (AGR2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -7.71E-01 p-value: 1.08E-130
More Results	Click to View More RNA-seq Results

Doxil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[116]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
In-vitro Model	MCF7-DoxR (Adriamycin-resistant cell line MCF7-DoxR)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
In-vivo Model	Once the tumor volume increased to about 1 cm3, six groups of MCF7 bearing mice (n = 10 in each group) were injected with PBS (0.1 ml, caudal vein) and adriamycin (0.1 ml, 10 mg/kg), respectively. When the tumor reached 1.5 cm in any direction (defined as event-free survival analysis), 10 mice in each group were selected to measure the tumor size and weight on the 12th day after adriamycin injection.
Response Summary	METTL3 can regulate the expression of MALAT1 through m6A, mediate the E2F1/Anterior gradient protein 2 homolog (AGR2) axis, and promote the adriamycin resistance of breast cancer.

ATP-dependent translocase ABCB1 (ABCB1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -1.24E+00 p-value: 2.14E-202
More Results	Click to View More RNA-seq Results

Doxil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[22]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
Cell Process	Cell growth and death
	Cell apoptosis
In-vitro Model	ADR-resistant MCF-7 (MCF-7/ADR) cells (Human breast cancer doxorubicin-resistant cell line)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
In-vivo Model	Cell suspensions (2 × 10⁶ cells/mL) made with MCF-7/ADR cells stably expressing METTL3 and/or miR-221-3p inhibitor were subcutaneously implanted into each mouse. One week later, xenografted mice were injected with 0.1 mL ADR (25 mg/kg, intraperitoneal injection) twice a week.
Response Summary	METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating pri-microRNA-221-3p maturation in a m6A-dependent manner. METTL3 knockdown was shown to reduce the expression of miR-221-3p by reducing pri-miR-221-3p m6A mRNA methylation, reducing the expression of ATP-dependent translocase ABCB1 (ABCB1) and BCRP, and inducing apoptosis. Identified the METTL3/miR-221-3p/HIPK2/Che-1 axis as a novel signaling event that will be responsible for resistance of BC cells to ADR.

DNA repair protein RAD51 homolog 1 (RAD51)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	HeLa cell line	Homo sapiens
Treatment: METTL3 knockdown HeLa cells Control: HeLa cells		GSE70061
Regulation		logFC: 2.32E+00 p-value: 1.62E-02
More Results	Click to View More RNA-seq Results

Doxil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[98]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
Pathway Response	Homologous recombination			hsa03440
Cell Process	Homologous recombination repair
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
In-vivo Model	Cells were trypsinized and resuspended in DMEM at a consistence of 1 × 10⁷ cells/ml. A total of 1 × 106 cells were injected into flank of mice. 27 days after injection, tumors were removed for paraffin-embedded sections.
Response Summary	Knockdown of METTL3 sensitized these breast cancer cells to Adriamycin (ADR; also named as doxorubicin) treatment and increased accumulation of DNA damage. Mechanically, we demonstrated that inhibition of METTL3 impaired HR efficiency and increased ADR-induced DNA damage by regulating m6A modification of EGF/RAD51 axis. METTL3 promoted EGF expression through m6A modification, which further upregulated DNA repair protein RAD51 homolog 1 (RAD51) expression, resulting in enhanced HR activity.

DNA-3-methyladenine glycosylase (ANPG/MPG)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Caco-2 cell line	Homo sapiens
Treatment: shMETTL3 Caco-2 cells Control: shNTC Caco-2 cells		GSE167075
Regulation		logFC: -6.00E-01 p-value: 3.04E-08
More Results	Click to View More RNA-seq Results

Temozolomide [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[69]
Responsed Disease	Glioblastoma		ICD-11: 2A00.00	Disease Info
Target Regulation	Down regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	DNA repair
In-vitro Model	U251 (Fibroblasts or fibroblast like cells)
	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
In-vivo Model	Subcutaneously injected shMETTL3 or shNC-expressing U87-MG-TMZ cells into BALB/c NOD mice. After confirmation of GBM implantation, mice were treated with TMZ (66 mg/kg/d, 5 d per week, for 3 cycles).
Response Summary	Two critical DNA repair genes (MGMT and DNA-3-methyladenine glycosylase (ANPG/MPG)) were m6A-modified by METTL3, whereas inhibited by METTL3 silencing or DAA-mediated total methylation inhibition, which is crucial for METTL3-improved temozolomide resistance in glioblastoma cells.

Epidermal growth factor receptor (EGFR)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	ARPE-19 cell line	Homo sapiens
Treatment: shMETTL3 ARPE-19 cells Control: shControl ARPE-19 cells		GSE202017
Regulation		logFC: -6.74E-01 p-value: 1.53E-03
More Results	Click to View More RNA-seq Results

PLX4032 [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[164]
Responsed Disease	Melanoma		ICD-11: 2C30	Disease Info
Target Regulation	Up regulation
Pathway Response	EGFR tyrosine kinase inhibitor resistance			hsa01521
Cell Process	Cell apoptosis
In-vitro Model	A375-R	Amelanotic melanoma	Homo sapiens	CVCL_6234
Response Summary	METTL3 increased the m6A modification of Epidermal growth factor receptor (EGFR) mRNA in A375R cells, which promoted its translation efficiency. Inhibiting METTL3 function to restore PLX4032 sensitivity in patients with melanoma.

Forkhead box protein O3 (FOXO3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 8.00E-01 p-value: 1.28E-68
More Results	Click to View More RNA-seq Results

Sorafenib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[167]
Responsed Disease	Hepatocellular carcinoma		ICD-11: 2C12.02	Disease Info
Target Regulation	Down regulation
Pathway Response	FoxO signaling pathway			hsa04068
Cell Process	Cell Transport
	Cell catabolism
	Cell autophagy
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	Hepa 1-6	Hepatocellular carcinoma of the mouse	Mus musculus	CVCL_0327
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	WRL 68	Endocervical adenocarcinoma	Homo sapiens	CVCL_0581
In-vivo Model	For the drug-resistant subcutaneous tumor models, drug administration was adopted when the tumors reached about 50 mm³ in size, at which point mice were randomized for treatment with DMSO(intraperitoneally) or sorafenib (50 mg/kg/every 2 days, intraperitoneally). For the patient-derived tumor xenograft model, drug administration began 4 weeks after tumors reached about 100 mm³ in size with sorafenib (50 mg/kg/every 3 days, intraperitoneally) or siCtrl/siMETTL3 intratumor injection.
Response Summary	METTL3 and Forkhead box protein O3 (FOXO3) levels are tightly correlated in hepatocellular carcinoma patients. In mouse xenograft models, METTL3 depletion significantly enhances sorafenib resistance of HCC by abolishing the identified METTL3-mediated FOXO3 mRNA stabilization, and overexpression of FOXO3 restores m6 A-dependent sorafenib sensitivity.

Hepatocyte growth factor receptor (c-Met/MET)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: 6.42E-01 p-value: 3.45E-17
More Results	Click to View More RNA-seq Results

Crizotinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[173]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	EGFR tyrosine kinase inhibitor resistance			hsa01521
In-vitro Model	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	NCI-H661	Lung large cell carcinoma	Homo sapiens	CVCL_1577
	NCI-H596	Lung adenosquamous carcinoma	Homo sapiens	CVCL_1571
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H358	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1559
	NCI-H292	Lung mucoepidermoid carcinoma	Homo sapiens	CVCL_0455
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1395	Lung adenocarcinoma	Homo sapiens	CVCL_1467
	EBC-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_2891
	Calu-3	Lung adenocarcinoma	Homo sapiens	CVCL_0609
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	HCC827 (3×10⁶) cells suspended in 100 uL of PBS were injected into the left inguen of female Balb/c nude mice (body weight 18-20 g; age 6 weeks; Beijing Huafukang Bioscience Co., Inc.). When the tumor volumes reached 50-100 mm³ on the 10th posttransplantation day, the mice were randomized into four groups (10 mice per group) and were intragastrically administered vehicle (normal saline), crizotinib (25 mg/kg body weight), chidamide (5 mg/kg), or the combination of the two drugs daily for 21 days. The tumor volumes and body weights of the mice were measured every 3 days.
Response Summary	Chidamide could decrease Hepatocyte growth factor receptor (c-Met/MET) expression by inhibiting mRNA N6-methyladenosine (m6A) modification through the downregulation of METTL3 and WTAP expression, subsequently increasing the crizotinib sensitivity of NSCLC cells in a c-MET-/HGF-dependent manner.

Gefitinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[174]
Responsed Disease	Lung cancer		ICD-11: 2C25	Disease Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vitro Model	NCI-H3255	Lung adenocarcinoma	Homo sapiens	CVCL_6831
Response Summary	METTL3 combines with Hepatocyte growth factor receptor (c-Met/MET) and causes the PI3K/AKT signalling pathway to be manipulated, which affects the sensitivity of lung cancer cells to gefitinib. METTL3 knockdown promotes apoptosis and inhibits proliferation of lung cancer cells.

Neurogenic locus notch homolog protein 2 (NOTCH2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: METTL3-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 1.84E+00 p-value: 2.61E-238
More Results	Click to View More RNA-seq Results

Melittin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[201]
Responsed Disease	Bladder cancer		ICD-11: 2C94	Disease Info
Target Regulation	Down regulation
Cell Process	miRNA maturation
	Cell apoptosis
In-vitro Model	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	EJ (Human bladder cancer cells)
	BIU-87	Human bladder cancer cells	Homo sapiens	CVCL_6881
In-vivo Model	For melittin treatment study, 4-week-old female BALB/c nude mice were subcutaneously injected with 1 × 10⁷ T24 or BIU87 cells.
Response Summary	METTL3 acts as a fate determinant that controls the sensitivity of bladder cancer cells to melittin treatment. Moreover, METTL3/miR-146a-5p/NUMB/Neurogenic locus notch homolog protein 2 (NOTCH2) axis plays an oncogenic role in bladder cancer pathogenesis and could be a potential therapeutic target for recurrent bladder cancer treatment.

Nuclear factor erythroid 2-related factor 2 (NFE2L2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	LX2 cell line	Homo sapiens
Treatment: shMETTL3 LX2 cells Control: shLuc LX2 cells		GSE207909
Regulation		logFC: -1.10E+00 p-value: 4.72E-06
More Results	Click to View More RNA-seq Results

Colistin [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[65]
Responsed Disease	Diseases of the urinary system	ICD-11: GC2Z	Disease Info
Target Regulation	Up regulation
Cell Process	Oxidative stress
	Cell apoptosis
In-vivo Model	The 60 female Kunming mice were divided into two groups (n = 30): control group (injection of physiological saline through the caudal vein) and colistin group (injection of 15 mg/kg colistin, twice a day, with an eight-hour interval).
Response Summary	m6A methylation was involved in oxidative stress-mediated apoptosis in the mechanism of colistin nephrotoxicity. METTL3-mediated M6A methylation modification is involved in colistin-induced nephrotoxicity through apoptosis mediated by Keap1/Nuclear factor erythroid 2-related factor 2 (NFE2L2) signaling pathway.

Nucleobindin-1 (NUCB1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	DKO-1 cell line	Homo sapiens
Treatment: METTL3 knockdown DKO-1 cell Control: DKO-1 cell		GSE182382
Regulation		logFC: -7.45E-01 p-value: 2.41E-03
More Results	Click to View More RNA-seq Results

Gemcitabine [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[204]
Responsed Disease	Pancreatic ductal adenocarcinoma		ICD-11: 2C10.0	Disease Info
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cell proliferation
Cell Process	Cell autophagy
In-vitro Model	SW1990	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	HEK293T	Normal	Homo sapiens	CVCL_0063
	CFPAC-1	Cystic fibrosis	Homo sapiens	CVCL_1119
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
In-vivo Model	5 × 10⁶ SW1990 cells expressing NUCB1 (oeNUCB1) or control vector (oeNC) were injected subcutaneously.
Response Summary	METTL3-mediated m6A modification on Nucleobindin-1 (NUCB1) 5'UTR via the reader YTHDF2 as a mechanism for NUCB1 downregulation in PDAC. This study revealed crucial functions of NUCB1 in suppressing proliferation and enhancing the effects of gemcitabine in pancreatic cancer cells.

Poly [ADP-ribose] polymerase 1 (PARP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	MOLM-13 cell line	Homo sapiens
Treatment: shMETTL3 MOLM13 cells Control: MOLM13 cells		GSE98623
Regulation		logFC: 1.69E+00 p-value: 1.05E-54
More Results	Click to View More RNA-seq Results

Oxaliplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[208]
Responsed Disease	Gastric cancer		ICD-11: 2B72	Disease Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Pathway Response	Signaling pathways regulating pluripotency of stem cells			hsa04550
Cell Process	RNA stability
Cell Process	Excision repair
In-vitro Model	SNU-719	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_5086
	MKN74	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_2791
	HEK293T	Normal	Homo sapiens	CVCL_0063
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
In-vivo Model	100,000 pLKO and PARP1-sh1 (PT1 and PT2) cells were mixed with matrix gel and inoculate into BALB/C nude mice, respectively. After 25 days, 6 organoid transplanted tumor mice were treated with oxaliplatin (Sellekchem, s1224) twice a week for 4 weeks at a dose of 5 mg/kg.
Response Summary	m6A methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting Poly [ADP-ribose] polymerase 1 (PARP1) mRNA stability which increases base excision repair pathway activity. METTTL3 enhances the stability of PARP1 by recruiting YTHDF1 to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA.

PR domain zinc finger protein 2 (PRDM2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Pancreatic islets	Mus musculus
Treatment: Mettl3 knockout mice Control: Mettl3 flox/flox mice		GSE155612
Regulation		logFC: 1.05E+00 p-value: 2.68E-04
More Results	Click to View More RNA-seq Results

Arsenite [Phase 2]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[27]
Responsed Disease	Solid tumour/cancer		ICD-11: 2A00-2F9Z	Disease Info
Target Regulation	Up regulation
Pathway Response	p53 signaling pathway			hsa04115
In-vitro Model	HaCaT	Normal	Homo sapiens	CVCL_0038
Response Summary	METTL3 significantly decreased m6A level, restoring p53 activation and inhibiting cellular transformation phenotypes in the arsenite-transformed cells. m6A downregulated the expression of the positive p53 regulator, PR domain zinc finger protein 2 (PRDM2), through the YTHDF2-promoted decay of PRDM2 mRNAs. m6A upregulated the expression of the negative p53 regulator, YY1 and MDM2 through YTHDF1-stimulated translation of YY1 and MDM2 mRNA. This study further sheds light on the mechanisms of arsenic carcinogenesis via RNA epigenetics.

Protein AATF (AATF/CHE1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Liver	Mus musculus
Treatment: Mettl3 knockout liver Control: Wild type liver cells		GSE198513
Regulation		logFC: -6.23E-01 p-value: 2.02E-10
More Results	Click to View More RNA-seq Results

Doxil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[22]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
Cell Process	Cell growth and death
	Cell apoptosis
In-vitro Model	ADR-resistant MCF-7 (MCF-7/ADR) cells (Human breast cancer doxorubicin-resistant cell line)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
In-vivo Model	Cell suspensions (2 × 10⁶ cells/mL) made with MCF-7/ADR cells stably expressing METTL3 and/or miR-221-3p inhibitor were subcutaneously implanted into each mouse. One week later, xenografted mice were injected with 0.1 mL ADR (25 mg/kg, intraperitoneal injection) twice a week.
Response Summary	METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating pri-microRNA-221-3p maturation in a m6A-dependent manner. METTL3 knockdown was shown to reduce the expression of miR-221-3p by reducing pri-miR-221-3p m6A mRNA methylation, reducing the expression of MDR1 and BCRP, and inducing apoptosis. Identified the METTL3/miR-221-3p/HIPK2/Protein AATF (AATF/CHE1) axis as a novel signaling event that will be responsible for resistance of BC cells to ADR.

Protein numb homolog (NUMB)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Treatment: METTL3 knockdown MDA-MB-231 cells Control: MDA-MB-231 cells		GSE70061
Regulation		logFC: 9.75E-01 p-value: 1.24E-03
More Results	Click to View More RNA-seq Results

Melittin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[201]
Responsed Disease	Bladder cancer		ICD-11: 2C94	Disease Info
Target Regulation	Down regulation
Cell Process	miRNA maturation
	Cell apoptosis
In-vitro Model	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	EJ (Human bladder cancer cells)
	BIU-87	Human bladder cancer cells	Homo sapiens	CVCL_6881
In-vivo Model	For melittin treatment study, 4-week-old female BALB/c nude mice were subcutaneously injected with 1 × 10⁷ T24 or BIU87 cells.
Response Summary	METTL3 acts as a fate determinant that controls the sensitivity of bladder cancer cells to melittin treatment. Moreover, METTL3/miR-146a-5p/Protein numb homolog (NUMB)/NOTCH2 axis plays an oncogenic role in bladder cancer pathogenesis and could be a potential therapeutic target for recurrent bladder cancer treatment.

Rho GTPase activating protein 5 (ARHGAP5)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Pancreatic islets	Mus musculus
Treatment: Mettl3 knockout mice Control: Mettl3 flox/flox mice		GSE155612
Regulation		logFC: 9.85E-01 p-value: 6.23E-05
More Results	Click to View More RNA-seq Results

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[215]
Responsed Disease	Gastric cancer		ICD-11: 2B72	Disease Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular Processes
	Transport and catabolism
In-vitro Model	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
Response Summary	ARHGAP5-AS1 also stabilized ARHGAP5 mRNA in the cytoplasm by recruiting METTL3 to stimulate m6A modification of Rho GTPase activating protein 5 (ARHGAP5) mRNA. As a result, ARHGAP5 was upregulated to promote chemoresistance and its upregulation was also associated with poor prognosis in gastric cancer. downregulation of ARHGAP5-AS1 in resistant cells evidently reversed the resistance to chemotherapeutic drugs including cisplatin (DDP), ADM, and 5-FU.

Fluorouracil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[215]
Responsed Disease	Gastric cancer		ICD-11: 2B72	Disease Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular processes
	Cellular transport, Cellular catabolism
In-vitro Model	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
Response Summary	ARHGAP5-AS1 also stabilized ARHGAP5 mRNA in the cytoplasm by recruiting METTL3 to stimulate m6A modification of Rho GTPase activating protein 5 (ARHGAP5) mRNA. As a result, ARHGAP5 was upregulated to promote chemoresistance and its upregulation was also associated with poor prognosis in gastric cancer. downregulation of ARHGAP5-AS1 in resistant cells evidently reversed the resistance to chemotherapeutic drugs including cisplatin (DDP), ADM, and 5-FU.

Adriamycin [Phase 3]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[215]
Responsed Disease	Gastric cancer		ICD-11: 2B72	Disease Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cellular processes
	Cellular transport, Cellular catabolism
In-vitro Model	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
Response Summary	ARHGAP5-AS1 also stabilized ARHGAP5 mRNA in the cytoplasm by recruiting METTL3 to stimulate m6A modification of Rho GTPase activating protein 5 (ARHGAP5) mRNA. As a result, ARHGAP5 was upregulated to promote chemoresistance and its upregulation was also associated with poor prognosis in gastric cancer. downregulation of ARHGAP5-AS1 in resistant cells evidently reversed the resistance to chemotherapeutic drugs including cisplatin (DDP), ADM, and 5-FU.

Ubiquitin-like-conjugating enzyme ATG3 (ATG3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by METTL3*
Cell Line	Liver	Mus musculus
Treatment: Mettl3-deficient liver Control: Wild type liver cells		GSE197800
Regulation		logFC: -1.62E+00 p-value: 2.55E-18
More Results	Click to View More RNA-seq Results

Sorafenib [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[17]
Responsed Disease	Hepatocellular carcinoma	ICD-11: 2C12.02	Disease Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including Ubiquitin-like-conjugating enzyme ATG3 (ATG3), ATG5, ATG7, ATG12, and ATG16L1.

Multidrug resistance-associated protein 1 (MRP1/ABCC1)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.47E+00	GSE60213

Imatinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[251]
Responsed Disease	Gastrointestinal stromal tumour		ICD-11: 2B5B	Disease Info
Target Regulation	Up regulation
In-vitro Model	GIST-T1	Gastrointestinal stromal tumor	Homo sapiens	CVCL_4976
In-vitro Model	GIST882	Gastrointestinal stromal tumor	Homo sapiens	CVCL_7044
In-vivo Model	For tumor growth assay, 4 × 10⁶ logarithmically growing GIST cells were transfected with T1S-vector, T1S-METTL3, 882S-vector, or 882S-METTL3 constructs, and subcutaneously injected in 100 ul of PBS into the flank of female nude mice(4-week-old). Mice were then randomly divided into 8 groups (n = 5 in each group): (1) injected with T1S-vector-harboring cells, and treated with imatinib (600 mg/l in drinking water); (2) injected with T1S-vector-harboring cells, and treated with imatinib (600 mg/l in drinking water) and MRP1 inhibitor (100 mg/l in drinking water); (3) injected with T1S-METTL3-harboring cells, and treated with imatinib (600 mg/l in drinking water); (4) injected with T1S-METTL3-harboring cells, and treated with imatinib (600 mg/l in drinking water) and MRP1 inhibitor (100 mg/l in drinking water); (5) injected with 882S-vector-harboring cells and treated with imatinib (600 mg/l in drinking water); (6) injected with 882S-vector-harboring cells, and treated with imatinib (600 mg/l in drinking water) and MRP1 inhibitor (100 mg/l in drinking water); (7) injected with 882S-METTL3-harboring cells, and treated with imatinib (600 mg/l in drinking water); and (8) injected with 882S-METTL3-harboring cells, and treated with imatinib (600 mg/l in drinking water) and MRP1 inhibitor (100 mg/l in drinking water).
Response Summary	METTL3, and the YTHDF1/eEF-1 complex mediate the translation of Multidrug resistance-associated protein 1 (MRP1/ABCC1) mRNA in an m6A-dependent manner to regulate the intracellular concentration of imatinib and drug resistance of gastrointestinal stromal tumor (GIST).

Long intergenic non-protein coding RNA 1273 (LINC01273)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 7.26E+00	GSE60213

Sorafenib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[256]
Responsed Disease	Hepatocellular carcinoma		ICD-11: 2C12.02	Disease Info
Target Regulation	Down regulation
In-vitro Model	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
Response Summary	Long intergenic non-protein coding RNA 1273 (LINC01273) was modified with m6A, METTL3 increased LINC01273 m6A modification, followed by LINC01273 decay in the presence of YTHDF2, a m6A 'reader'. And LINC01273 plays a key role in sorafenib resistant HCC cells.

NIFK antisense RNA 1 (NIFK-AS1)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 7.43E+00	GSE60213

Sorafenib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[258]
Responsed Disease	Hepatocellular carcinoma		ICD-11: 2C12.02	Disease Info
Target Regulation	Up regulation
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	THLE-3	Normal	Homo sapiens	CVCL_3804
In-vivo Model	For the PDX model, fresh patient HCC tissues were cut into fragments with a volume of 3 × 3 mm³ and then implanted subcutaneously into the flanks of nude mice. The mice were given sorafenib (30 mg/kg) or vehicle orally twice a week for 24 days. This procedure was approved by the Ethics Committee of Jinling Hospital.
Response Summary	Identified the lncRNA NIFK antisense RNA 1 (NIFK-AS1) as being highly expressed in hepatocellular carcinoma tissues and cells, promotes disease progression and sorafenib resistance, and showed this up-regulation resulted from METTL3-dependent m6A methylation.

Small nucleolar RNA host gene 3 (SNHG3)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and METTL3*
Cell Line	MDA-MB-231	Homo sapiens
Regulation	logFC: 1.17E+00	GSE60213

Pt [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[259]
Responsed Disease	Esophageal cancer		ICD-11: 2B70	Disease Info
Target Regulation	Up regulation
Cell Process	Cellular Processes
	Cell growth and death
	Cell apoptosis
In-vitro Model	Eca-9706 (Esophageal carcinoma cell line)
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
In-vivo Model	Used 1 × 10⁶ SNHG3 knocked down KY-SE150 cells and NC lentivirus to inject into the right flank of mice to generate xenografts.
Response Summary	Platinum can increase the overall m6A level of esophageal cancer. Small nucleolar RNA host gene 3 (SNHG3)/miR-186-5p, induced by platinum, was involved in regulating m6A level by targeting METTL3. miR-186-5p binds to the 3'UTR of METTL3 to inhibit its expression. Our manuscript has provided clues that regulating m6A level was a novel way to enhance the platinum efficacy.

E3 ubiquitin-protein ligase TRIM11 (TRIM11)

Target Gene

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[14]
Responsed Disease	Nasopharyngeal carcinoma		ICD-11: 2B6B	Disease Info
Target Regulation	Down regulation
Pathway Response	ABC transporters			hsa02010
	Wnt signaling pathway			hsa04310
	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Ubiquitination degradation
In-vitro Model	CNE-1	Normal	Homo sapiens	CVCL_6888
	CNE-2	Nasopharyngeal carcinoma	Homo sapiens	CVCL_6889
In-vivo Model	A total of 2 × 10⁶ cells was mixed with 0.2 ml PBS (pH 7.4) and 30% (v/v) Matrigel matrix (BD Biosciences).
Response Summary	TRIM11 regulates nasopharyngeal carcinoma drug resistance by positively modulating the Daple/beta-catenin/E3 ubiquitin-protein ligase TRIM11 (TRIM11) signaling pathway. TRIM11 enhanced the multidrug resistance in NPC by inhibiting apoptosis in vitro and promoting cisplatin (DDP) resistance in vivo. METTL3-mediated m6A modification caused the upregulation of TRIM11 via IGF2BP2 in NPC drug-resistant cells.

RAD51-associated protein 1 (RAD51AP1)

Target Gene

Fluorouracil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[273]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Up regulation
In-vitro Model	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
Response Summary	METTL3 augmented 5?FU?induced DNA damage and overcame 5?FU?resistance in HCT?8R cells, which could be mimicked by inhibition of RAD51-associated protein 1 (RAD51AP1). The present study revealed that the METTL3/RAD51AP1 axis plays an important role in the acquisition of 5?FU resistance in CRC.

DBH antisense RNA 1 (Lnc_DBH-AS1)

Target Gene

Gemcitabine [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[274]
Responsed Disease	Pancreatic cancer		ICD-11: 2C10	Disease Info
In-vitro Model	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	HPDE	Normal	Homo sapiens	CVCL_4376
	CFPAC-1	Cystic fibrosis	Homo sapiens	CVCL_1119
	Canpan-2 (Pancreatic cancer cell line)
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
Response Summary	DBH antisense RNA 1 (Lnc_DBH-AS1) expression in pancreatic cancer(PC) was found to be linked to the METTL3-dependent m6A methylation of the lncRNA. MechanisticallyDBH-AS1 was able to increase PC cell sensitivity to gemcitabine by sequestering miR-3163 and thus upregulating USP44 in these tumor cells.

microRNA let-7b (MIRLET7B)

Target Gene

Osimertinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[282]
Responsed Disease	Lung cancer		ICD-11: 2C25	Disease Info
Pathway Response	Notch signaling pathway			hsa04330
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	H1975OR (Osimertinib resistant H1975 cells)
	HCC827OR (Osimertinib resistant HCC827 cells)
Response Summary	the participation of Metformin decreased the bindings of DNMT3a/b to the METTL3 promoter with the help of the readers of NKAP and HNRNPA2B1.the mediation of m6A formation on pri-Let-7b processing increased the mature microRNA let-7b (MIRLET7B), whose key role is to suppress the Notch signaling and to re-captivate the Osimertinib treatment.The findings open up future drug development, targeting this pathway for lung cancer patients.

hsa-miR-146a-5p

Target Gene

Melittin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[201]
Responsed Disease	Bladder cancer		ICD-11: 2C94	Disease Info
Target Regulation	Up regulation
Cell Process	miRNA maturation
	Cell apoptosis
In-vitro Model	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	EJ (Human bladder cancer cells)
	BIU-87	Human bladder cancer cells	Homo sapiens	CVCL_6881
In-vivo Model	For melittin treatment study, 4-week-old female BALB/c nude mice were subcutaneously injected with 1 × 10⁷ T24 or BIU87 cells.
Response Summary	METTL3 acts as a fate determinant that controls the sensitivity of bladder cancer cells to melittin treatment. Moreover, METTL3/hsa-miR-146a-5p/NUMB/NOTCH2 axis plays an oncogenic role in bladder cancer pathogenesis and could be a potential therapeutic target for recurrent bladder cancer treatment.

hsa-miR-181d-5p

Target Gene

Fluorouracil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[88]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Up regulation
In-vitro Model	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vivo Model	A tumor-bearing model was established by subcutaneously injecting 100 ul HT29 cells (5×10⁶) followed by an intravenous injection of CAFs-derived exosomes (50 ug/mouse every three days) into the tail vein of the mice. An intraperitoneal injection of 5-FU (50 mg/kg, every week) was administered on day 12.
Response Summary	METTL3?dependent m6A methylation was upregulated in CRC to promote the processing of miR?181d?5p by DGCR8. This led to increased hsa-miR-181d-5p expression, which inhibited the 5?FU sensitivity of CRC cells by targeting NCALD.

hsa-miR-186-5p

Target Gene

Pt [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[259]
Responsed Disease	Esophageal cancer		ICD-11: 2B70	Disease Info
Target Regulation	Up regulation
Cell Process	Cellular Processes
	Cell growth and death
	Cell apoptosis
In-vitro Model	Eca-9706 (Esophageal carcinoma cell line)
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
In-vivo Model	Used 1 × 10⁶ SNHG3 knocked down KY-SE150 cells and NC lentivirus to inject into the right flank of mice to generate xenografts.
Response Summary	Platinum can increase the overall m6A level of esophageal cancer. SNHG3/hsa-miR-186-5p, induced by platinum, was involved in regulating m6A level by targeting METTL3. miR-186-5p binds to the 3'UTR of METTL3 to inhibit its expression. Our manuscript has provided clues that regulating m6A level was a novel way to enhance the platinum efficacy.

hsa-miR-1914-3p

Target Gene

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[126]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 10⁶ lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-hsa-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.

hsa-miR-221-3p

Target Gene

Doxil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[22]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
Cell Process	Cell growth and death
	Cell apoptosis
In-vitro Model	ADR-resistant MCF-7 (MCF-7/ADR) cells (Human breast cancer doxorubicin-resistant cell line)
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MCF-10A	Normal	Homo sapiens	CVCL_0598
In-vivo Model	Cell suspensions (2 × 10⁶ cells/mL) made with MCF-7/ADR cells stably expressing METTL3 and/or miR-221-3p inhibitor were subcutaneously implanted into each mouse. One week later, xenografted mice were injected with 0.1 mL ADR (25 mg/kg, intraperitoneal injection) twice a week.
Response Summary	METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating hsa-miR-221-3p maturation in a m6A-dependent manner. METTL3 knockdown was shown to reduce the expression of miR-221-3p by reducing pri-miR-221-3p m6A mRNA methylation, reducing the expression of MDR1 and BCRP, and inducing apoptosis. Identified the METTL3/miR-221-3p/HIPK2/Che-1 axis as a novel signaling event that will be responsible for resistance of BC cells to ADR.

hsa_circ_0008399

Target Gene

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[298]
Responsed Disease	Bladder cancer		ICD-11: 2C94	Disease Info
Target Regulation	Up regulation
Pathway Response	Protein export			hsa03060
Cell Process	Eukaryotic translation
Cell Process	Cell apoptosis
In-vitro Model	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
	RT-4	Bladder carcinoma	Homo sapiens	CVCL_0036
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
In-vivo Model	Chose 4-week-old female BALB/c nude mice for tumor xenograft experiments, which randomly were divided into four groups (n = 5 per group). Bladder cancer cells (3 × 10⁶) were subcutaneously injected into the right axilla of the nude mice.
Response Summary	Circ0008399 bound WTAP to promote formation of the WTAP/METTL3/METTL14 m6A methyltransferase complex, reduce cisplatin sensitivity in bladder cancer, implicating the potential therapeutic value of targeting this axis.

Circ_ASK1

Target Gene

Gefitinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[303]
Responsed Disease	Lung adenocarcinoma		ICD-11: 2C25.0	Disease Info
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
	SK-LU-1	Lung adenocarcinoma	Homo sapiens	CVCL_0629
	NCI-H1993	Lung adenocarcinoma	Homo sapiens	CVCL_1512
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	16HBE14o-	Normal	Homo sapiens	CVCL_0112
In-vivo Model	Established a xenograft model in BALB/c nude mice by inoculating HCC827-GR cells transfected with the constructs for circASK1 silencing, ASK1-272a.a overexpression and ASK1-272a.a overexpression/circASK1 knockdown
Response Summary	Increased YTHDF2-mediated endoribonucleolytic cleavage of m6A-modified Circ_ASK1 accounts for its downregulation in gefitinib-resistant cells. Either METTL3 silencing or YTHDF2 silencing suppressed the decay of circASK1 in HCC827-GR cells. This study provides a novel therapeutic target to overcome gefitinib resistance in LUAD patients.

miR-17-92

Target Gene

Everolimus [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[305]
Responsed Disease	Gastric cancer		ICD-11: 2B72	Disease Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	miRNA maturation
In-vitro Model	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
In-vivo Model	For subcutaneous xenograft models, 0.1 mL of cell suspension containing 10⁶ cells were injected subcutaneously into the right flank of mice (n = 6 for each group).
Response Summary	In gastric cancer, m6A facilitated processing of pri-miR-17-92 into the miR-17-92 cluster through an m6A/DGCR8-dependent mechanism. METTL3-high tumors showed preferred sensitivity to an mTOR inhibitor, everolimus.

Unspecific Target Gene

Arsenite [Phase 2]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene		[310]
Cell Process	Cell apoptosis
In-vitro Model	HBE (Human bronchial epithelial cell line)
Response Summary	m6A modification on RNA was significantly increased in arsenite-transformed cells and this modification was synergistically regulated by METTL3, METTL14, WTAP and FTO. Demonstrated the significant role of m6A in the prevention of tumor occurrence and progression induced by arsenite.

Temozolomide [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[312]
Responsed Disease	Glioblastoma		ICD-11: 2A00.00	Disease Info
Pathway Response	RNA degradation			hsa03018
Cell Process	mRNA decay
In-vitro Model	U251 (Fibroblasts or fibroblast like cells)
	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
In-vivo Model	Used to inject 10 uL of the U87 MG-TMZ_R-luc cell suspension in the striatum at a depth of 3 mm from the dural surface. One week after the injection of the tumor cells, 40 mg/kg/day of TMZ in saline was administered for over 2 weeks by intraperitoneal injection.
Response Summary	Uncover the fundamental mechanisms underlying the interplay of m6 A RNA modification and histone modification in Temozolomide resistance and emphasize the therapeutic potential of targeting the SOX4/EZH2/METTL3 axis in the treatment of TMZ-resistant glioblastoma.

Gemcitabine [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[318]
Responsed Disease	Pancreatic cancer		ICD-11: 2C10	Disease Info
Pathway Response	Adipocytokine signaling pathway			hsa04920

Cell Process	Epithelial-mesenchymal transition
In-vitro Model	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	HDE-CT cell line (A normal human pancreatic cell line)
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
Response Summary	Lasso regression identified a six-m6A-regulator-signature prognostic model (KIAA1429, HNRNPC, METTL3, YTHDF1, IGF2BP2, and IGF2BP3). Gene set enrichment analysis revealed m6A regulators (KIAA1429, HNRNPC, and IGF2BP2) were related to multiple biological behaviors in pancreatic cancer, including adipocytokine signaling, the well vs. poorly differentiated tumor pathway, tumor metastasis pathway, epithelial mesenchymal transition pathway, gemcitabine resistance pathway, and stemness pathway.

Ethyl ester form of meclofenamic acid [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[342]
Responsed Disease	Male infertility		ICD-11: GB04	Disease Info
Cell Process	Cell cycle
	Cell proliferation
In-vitro Model	GC-1 spg	Normal	Mus musculus	CVCL_8872
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Mouse GC-1 spg cells were treated with the ester form of meclofenamic acid (MA2) to inhibit the demethylase activity of FTO.
Response Summary	METTL3, METTL14, ALKBH5 and YTHDC2 are involved in the regulation of spermatogenesis and oogenesis. MA2 affected CDKs expression through the m6A-dependent mRNA degradation pathway, and thus repressed spermatogonial proliferation. Additionally, mutation of the predicted m6A sites in the Cdk2-3'UTR could mitigated the degradation of CDK2 mRNA after MA2 treatment.

Click to View Potential Drug Response of This Regulator

Xenobiotics Compound(s) Regulating the m6A Methylation Regulator

Compound Name	MA2	Approved
Synonyms	Ethyl ester form of meclofenamic acid (MA) Click to Show/Hide
Description	Knockdown of METTL3 or METTL14 induced changes in mRNA m6A enrichment and altered mRNA expression of genes (e.g.,ADAM19) with critical biological functions inGSCs. Treatment with MA2, a chemical inhibitor of FTO, dramatically suppressed GSC-induced tumorigenesis and prolonged lifespan in GSC-grafted animals.	[194]
Compound Name	Simovil	Approved
Synonyms	Cholestat; Coledis; Colemin; Corolin; Denan; Labistatin; Lipex; Lipovas; Lodales; Medipo; Nivelipol; Pantok; Rendapid; Simovil; Simvastatina; Simvastatine; Simvastatinum; Sinvacor; Sivastin; Synvinolin; Vasotenal; Zocor; Zocord; Simvast CR; Simvastatina [Spanish]; Simvastatine [French]; Simvastatinum [Latin]; MK 0733; MK 733; MK733; TNP00259; DRG-0320; KS-1113; L 644128-000U; MK-0733; MK-733; Simcard (TN); Simlup (TN); Simvacor (TN); Simvastatin & Primycin; Simvastatin, Compactin; Zocor (TN); Simvastatin [USAN:INN:BAN]; Simvastatin (JAN/USP/INN); Zocor, Simlup, Simcard, Simvacor, Simvoget, Zorced, Simvastatin; [(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] 2,2-dimethylbutanoate; Butanoic acid, 2,2-dimethyl-, (1S,3R,7S,8S,8aR)-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-[(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl]ethyl]-1-naphthalenyl ester; Butanoic acid, 2,2-dimethyl-, (1S,3R,7S,8S,8aR)-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-(2-((2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl)-1-naphthalenyl ester; Butanoic acid, 2,2-dimethyl-, (1S,3R,7S,8S,aR)-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-(2-((2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl)-1-naphthalenyl ester; (1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2,2-dimethylbutanoate; Butanoic acid, 2,2-dimethyl-,1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)-ethyl]-1-naphthalenyl ester, [1S-[1 alpha,3 alpha,7 beta,8 beta(2S,4S*),-8a beta; 2,2-Dimethylbutanoic acid (1S,3R,7S,8S,8aR)-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-[(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl]ethyl]-1-naphthalenyl ester; 2,2-Dimethylbutyric acid, 8-ester with (4R,6R)-6-(2-((1S,2S,6R,8S,8aR)-1,2,6,7,8,8a-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthyl)ethyl)tetrahydro-4-hydroxy-2H-pyran-2-one Click to Show/Hide
External link	CID: 54454 TTD: D0H0ND DrugBank: DB00641
Description	Simvastatin induces METTL3 down-regulation in lung cancer tissues, which further influences EMT via m6A modification onEZH2 mRNA and thus inhibits the malignant progression oflung cancer.	[59]
Compound Name	Rapamycin	Approved
Synonyms	Rapamune; Rapamycin (Sirolimus); AY-22989; Rapammune; sirolimusum; WY-090217; RAPA; Antibiotic AY 22989; AY 22989; UNII-W36ZG6FT64; CCRIS 9024; CHEBI:9168; SILA 9268A; W36ZG6FT64; HSDB 7284; C51H79NO13; NSC 226080; DE-109; NCGC00021305-05; DSSTox_CID_3582; DSSTox_RID_77091; DSSTox_GSID_23582; Cypher; Supralimus; Wy 090217; Perceiva; RAP; RPM; Rapamycin from Streptomyces hygroscopicus; SIIA 9268A; LCP-Siro; MS-R001; Rapamune (TN); Rapamycin (TN); Sirolimus (RAPAMUNE); Rapamycin C-7, analog 4; Sirolimus (USAN/INN); Sirolimus [USAN:BAN:INN]; Sirolimus, Rapamune,Rapamycin; Heptadecahydro-9,27-dihydroxy-3-[(1R)-2-[(1S,3R,4R)-4-hydroxy; 23,27-Epoxy-3H-pyrido(2,1-c)(1,4)oxaazacyclohentriacontine; 23,27-Epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine; 23,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29; 3H-pyrido(2,1-c)(1,4)oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone; Sirolimus (MTOR inhibitor) Click to Show/Hide
External link	CID: 5284616 TTD: D03LJR DrugBank: DB00877
Description	METTL3 promotes the progression ofretinoblastoma throughPI3K/AKT/mTOR pathways in vitro and in vivo. METTL3 has an impact on the PI3K-AKT-mTOR-P70S6K/4EBP1 pathway. The cell proliferation results show that the stimulatory function of METTL3 is lost after rapamycin treatment.	[44]
Compound Name	BEZ235	Phase 2
Synonyms	BEZ-235; S14-0511; NVP-BEZ-235; NVP-BEZ235, BEZ235; 2-(4-(2,3-dihydro-3-methyl-2-oxo-8-(quinolin-3-yl)imidazo[4,5-c]quinolin-1-yl)phenyl)-2-methylpropanenitrile Click to Show/Hide
External link	CID: 11977753 TTD: D0VG0D DrugBank: DB11651
Description	METTL3 plays a carcinogenic role in human EC progression partially throughAKT signaling pathways, suggesting that METTL3 serves as a potential therapeutic target foresophageal cancer therapy. A double-effect inhibitor (BEZ235) inhibited AKT and mTOR phosphorylation and hindered the effect of METTL3 overexpression on the proliferation and migration of Eca-109 and KY-SE150 cells.	[212]
Compound Name	STM2457	Preclinical
Synonyms	STM-2457; SCHEMBL22499068; GTPL11529; CHEBI:172325; EX-A5018; STM 2457; s9870; HY-134836; N-[(6-{[(cyclohexylmethyl)amino]methyl}imidazo[1,2-a]pyridin-2-yl)methyl]-4-oxo-4H-pyrido[1,2-a]pyrimidine-2-carboxamide; N-[[6-[(cyclohexylmethylamino)methyl]imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxopyrido[1,2-a]pyrimidine-2-carboxamide Click to Show/Hide
External link	CID: 155167581
Description	inhibition of METTL3 by STM2457 targets key stem cell populations ofacute myeloid leukaemia and reverses the AML phenotype, preventing or slowing the development of AML in re-transplantation experiments.	[315]
Compound Name	N~2~-hexyl-6,7-dimethoxy-N~4~-(1-methylpiperidin-4-yl)quinazoline-2,4-diamine	Investigative
Synonyms	CHEMBL4086403; SCHEMBL23260478; MS012; BDBM50501525; MS 012; MS-012; N~2~-hexyl-6,7-dimethoxy-N~4~-(1-methylpiperidin-4-yl)quinazoline-2,4-diamine; 2089617-83-2 Click to Show/Hide
External link	CID: 137348638
Activity	IC50=7±2 nM	[347]
Compound Name	6,7-Dimethoxy-N-(1-Methylpiperidin-4-Yl)-2-(Morpholin-4-Yl)quinazolin-4-Amine	Investigative
Synonyms	CHEMBL571717; 6,7-Dimethoxy-N-(1-Methylpiperidin-4-Yl)-2-(Morpholin-4-Yl)quinazolin-4-Amine; 7L6; SCHEMBL15280520; BDBM50300032; NCGC00185861-01; 6,7-dimethoxy-N-(1-methylpiperidin-4-yl)-2-morpholinoquinazolin-4-amine Click to Show/Hide
External link	CID: 44605026
Activity	IC50=13 ± 4 nM	[347]
Compound Name	Cycloleucine	Investigative
Synonyms	1-Aminocyclopentanecarboxylic acid; 52-52-8; 1-Aminocyclopentane-1-carboxylic acid; Cycloleucin; 1-Amino-1-cyclopentanecarboxylic acid; 1-Amino-1-carboxycyclopentane; 1-Amino-cyclopentanecarboxylic acid; CYCLO-LEUCINE; Cyclopentanecarboxylic acid, 1-amino-; NSC 1026; CB 1639; X 201; UNII-0TQU7668EI; 1-Aminocyclopentanecarboxylate; HSDB 5195; WR 14,997; NSC1026; 1-amino cyclopentane carboxylic acid; EINECS 200-144-6; BRN 0636626; aminocyclopentanecarboxylic acid; Cyclopentanecarboxylic acid, 1-amino-, L-; AI3-26442 Click to Show/Hide
External link	CID: 2901 TTD: D0P0GT DrugBank: DB04620
Description	METTL3-mediated m6A RNA methylation modulatesuveal melanoma cell proliferation, migration, and invasion by targetingc-Met. Cycloleucine (Cyc) was used to block m6 A methylation in UM cells.	[175]
Compound Name	AdoHcy	Investigative
Synonyms	S-Adenosyl-L-homocysteine; S-adenosylhomocysteine; S-adenosyl-L-homocysteine; 979-92-0; AdoHcy; S-(5'-adenosyl)-L-homocysteine; adenosylhomocysteine; Formycinylhomocysteine; Adenosyl-L-homocysteine; S-(5'-deoxyadenosin-5'-yl)-L-homocysteine; 2-S-adenosyl-L-homocysteine; 5'-Deoxy-S-adenosyl-L-homocysteine; S-adenosyl-homocysteine; S-Adenosyl Homocysteine; L-S-Adenosylhomocysteine; L-Homocysteine, S-(5'-deoxyadenosin-5'-yl)-; adenosylhomo-cys; adenosyl-homo-cys; UNII-8K31Q2S66S; (S)-5'-(S)-(3-Amino-3-carboxypropyl)-5'-thioadenosine; BRN 5166233; SAH; S-Adenosylhomocysteine; S-Adenosyl-L-Homocysteine Click to Show/Hide
External link	CID: 439155 TTD: D09CLP DrugBank: DB01752
Description	Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) inducedtemporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by TNF-alpha stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Bcl2 signal axis which provides promising therapeutic strategy fortemporomandibular joint osteoarthritis.	[10]

References

Ref 1	RNA m6A methyltransferase METTL3 regulates invasiveness of melanoma cells by matrix metallopeptidase 2. Melanoma Res. 2019 Aug;29(4):382-389. doi: 10.1097/CMR.0000000000000580.
Ref 2	METTL3-mediated m6A methylation of ASPM drives hepatocellular carcinoma cells growth and metastasis. J Clin Lab Anal. 2021 Sep;35(9):e23931. doi: 10.1002/jcla.23931. Epub 2021 Aug 16.
Ref 3	METTL3 promotes tumour development by decreasing APC expression mediated by APC mRNA N(6)-methyladenosine-dependent YTHDF binding. Nat Commun. 2021 Jun 21;12(1):3803. doi: 10.1038/s41467-021-23501-5.
Ref 4	The m(6)A methyltransferase METTL3 promotes bladder cancer progression via AFF4/NF-KappaB/MYC signaling network. Oncogene. 2019 May;38(19):3667-3680. doi: 10.1038/s41388-019-0683-z. Epub 2019 Jan 18.
Ref 5	The m(6)A Methylation-Regulated AFF4 Promotes Self-Renewal of Bladder Cancer Stem Cells. Stem Cells Int. 2020 Jul 2;2020:8849218. doi: 10.1155/2020/8849218. eCollection 2020.
Ref 6	Deficiency of Mettl3 in Bladder Cancer Stem Cells Inhibits Bladder Cancer Progression and Angiogenesis. Front Cell Dev Biol. 2021 Feb 18;9:627706. doi: 10.3389/fcell.2021.627706. eCollection 2021.
Ref 7	Knockdown of METTL3 inhibits enterovirus 71-induced apoptosis of mouse Schwann cell through regulation of autophagy. Pathog Dis. 2021 Jul 28;79(6):ftab036. doi: 10.1093/femspd/ftab036.
Ref 8	METTL3 Promotes the Proliferation and Mobility of Gastric Cancer Cells. Open Med (Wars). 2019 Mar 2;14:25-31. doi: 10.1515/med-2019-0005. eCollection 2019.
Ref 9	The N(6)-methyladenosine (m(6)A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells. Nat Med. 2017 Nov;23(11):1369-1376. doi: 10.1038/nm.4416. Epub 2017 Sep 18.
Ref 10	Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through mediating Bcl2 stability via Ythdf1-mediated m(6)A modification. Bone. 2022 Jan;154:116182. doi: 10.1016/j.bone.2021.116182. Epub 2021 Sep 13.
Ref 11	METTL3?mediated m6A modification of Bcl?2 mRNA promotes non?small cell lung cancer progression. Oncol Rep. 2021 Aug;46(2):163. doi: 10.3892/or.2021.8114. Epub 2021 Jun 16.
Ref 12	N6-methyladenosine METTL3 promotes the breast cancer progression via targeting Bcl-2. Gene. 2020 Jan 5;722:144076. doi: 10.1016/j.gene.2019.144076. Epub 2019 Aug 24.
Ref 13	DARS-AS1 recruits METTL3/METTL14 to bind and enhance DARS mRNA m(6)A modification and translation for cytoprotective autophagy in cervical cancer. RNA Biol. 2022 Jan;19(1):751-763. doi: 10.1080/15476286.2022.2079889.
Ref 14	TRIM11 facilitates chemoresistance in nasopharyngeal carcinoma by activating the Beta-catenin/ABCC9 axis via p62-selective autophagic degradation of Daple. Oncogenesis. 2020 May 7;9(5):45. doi: 10.1038/s41389-020-0229-9.
Ref 15	The RNA N6-Methyladenosine Methyltransferase METTL3 Promotes the Progression of Kidney Cancer via N6-Methyladenosine-Dependent Translational Enhancement of ABCD1. Front Cell Dev Biol. 2021 Sep 23;9:737498. doi: 10.3389/fcell.2021.737498. eCollection 2021.
Ref 16	Silencing METTL3 inhibits the proliferation and invasion of osteosarcoma by regulating ATAD2. Biomed Pharmacother. 2020 May;125:109964. doi: 10.1016/j.biopha.2020.109964. Epub 2020 Feb 7.
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Ref 45	METTL3 mediates osteoblast apoptosis by regulating endoplasmic reticulum stress during LPS-induced inflammation. Cell Signal. 2022 Jul;95:110335. doi: 10.1016/j.cellsig.2022.110335. Epub 2022 Apr 21.
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Ref 55	N(6)-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification. Cell Death Dis. 2020 Oct 24;11(10):911. doi: 10.1038/s41419-020-03071-y.
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Ref 83	METTL3 regulates alternative splicing of MyD88 upon the lipopolysaccharide-induced inflammatory response in human dental pulp cells. J Cell Mol Med. 2018 May;22(5):2558-2568. doi: 10.1111/jcmm.13491. Epub 2018 Mar 4.
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Ref 96	METTL3-mediated N (6)-methyladenosine modification governs pericyte dysfunction during diabetes-induced retinal vascular complication. Theranostics. 2022 Jan 1;12(1):277-289. doi: 10.7150/thno.63441. eCollection 2022.
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Ref 98	METTL3 promotes homologous recombination repair and modulates chemotherapeutic response in breast cancer by regulating the EGF/RAD51 axis. Elife. 2022 May 3;11:e75231. doi: 10.7554/eLife.75231.
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Ref 103	METTL3 restrains papillary thyroid cancer progression via m(6)A/c-Rel/IL-8-mediated neutrophil infiltration. Mol Ther. 2021 May 5;29(5):1821-1837. doi: 10.1016/j.ymthe.2021.01.019. Epub 2021 Jan 21.
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Ref 105	N (6)-Methyladenosine modification of hepatitis B and C viral RNAs attenuates host innate immunity via RIG-I signaling. J Biol Chem. 2020 Sep 11;295(37):13123-13133. doi: 10.1074/jbc.RA120.014260. Epub 2020 Jul 27.
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Ref 122	The m6A methyltransferase METTL3 promotes the stemness and malignant progression of breast cancer by mediating m6A modification on SOX2. J BUON. 2021 Mar-Apr;26(2):444-449.
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Ref 125	RNA m6A methylation promotes the formation of vasculogenic mimicry in hepatocellular carcinoma via Hippo pathway. Angiogenesis. 2021 Feb;24(1):83-96. doi: 10.1007/s10456-020-09744-8. Epub 2020 Sep 13.
Ref 126	m(6)A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-YAP axis to induce NSCLC drug resistance and metastasis. J Hematol Oncol. 2019 Dec 9;12(1):135. doi: 10.1186/s13045-019-0830-6.
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Ref 132	METTL3-mediated m(6)A modification of ZBTB4 mRNA is involved in the smoking-induced EMT in cancer of the lung. Mol Ther Nucleic Acids. 2020 Dec 10;23:487-500. doi: 10.1016/j.omtn.2020.12.001. eCollection 2021 Mar 5.
Ref 133	METTL3-mediated N6-methyladenosine modification is critical for epithelial-mesenchymal transition and metastasis of gastric cancer. Mol Cancer. 2019 Oct 13;18(1):142. doi: 10.1186/s12943-019-1065-4.
Ref 134	m(6)A-mediated ZNF750 repression facilitates nasopharyngeal carcinoma progression. Cell Death Dis. 2018 Dec 5;9(12):1169. doi: 10.1038/s41419-018-1224-3.
Ref 135	RNA m(6)A Methyltransferase METTL3 Promotes The Growth Of Prostate Cancer By Regulating Hedgehog Pathway. Onco Targets Ther. 2019 Nov 5;12:9143-9152. doi: 10.2147/OTT.S226796. eCollection 2019.
Ref 136	m(6)A methyltransferase METTL3-mediated lncRNA FOXD2-AS1 promotes the tumorigenesis of cervical cancer. Mol Ther Oncolytics. 2021 Jul 21;22:574-581. doi: 10.1016/j.omto.2021.07.004. eCollection 2021 Sep 24.
Ref 137	N(6) -Methyladenosine Regulates mRNA Stability and Translation Efficiency of KRT7 to Promote Breast Cancer Lung Metastasis. Cancer Res. 2021 Jun 1;81(11):2847-2860. doi: 10.1158/0008-5472.CAN-20-3779. Epub 2021 Apr 1.
Ref 138	LncRNA LBX2-AS1 promotes colorectal cancer progression and 5-fluorouracil resistance. Cancer Cell Int. 2021 Sep 17;21(1):501. doi: 10.1186/s12935-021-02209-y.
Ref 139	LNCAROD is stabilized by m6A methylation and promotes cancer progression via forming a ternary complex with HSPA1A and YBX1 in head and neck squamous cell carcinoma. Mol Oncol. 2020 Jun;14(6):1282-1296. doi: 10.1002/1878-0261.12676. Epub 2020 Apr 13.
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Ref 141	M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma. J Hematol Oncol. 2020 Jan 8;13(1):5. doi: 10.1186/s13045-019-0839-x.
Ref 142	m(6)A-induced LINC00958 promotes breast cancer tumorigenesis via the miR-378a-3p/YY1 axis. Cell Death Discov. 2021 Feb 2;7(1):27. doi: 10.1038/s41420-020-00382-z.
Ref 143	METTL3 enhances the stability of MALAT1 with the assistance of HuR via m6A modification and activates NF-KappaB to promote the malignant progression of IDH-wildtype glioma. Cancer Lett. 2021 Jul 28;511:36-46. doi: 10.1016/j.canlet.2021.04.020. Epub 2021 Apr 29.
Ref 144	METTL3-dependent MALAT1 delocalization drives c-Myc induction in thymic epithelial tumors. Clin Epigenetics. 2021 Sep 16;13(1):173. doi: 10.1186/s13148-021-01159-6.
Ref 145	m(6)A-induced lncRNA MALAT1 aggravates renal fibrogenesis in obstructive nephropathy through the miR-145/FAK pathway. Aging (Albany NY). 2020 Mar 23;12(6):5280-5299. doi: 10.18632/aging.102950. Epub 2020 Mar 23.
Ref 146	Changes and relationship of N(6)-methyladenosine modification and long non-coding RNAs in oxidative damage induced by cadmium in pancreatic Beta-cells. Toxicol Lett. 2021 Jun 1;343:56-66. doi: 10.1016/j.toxlet.2021.02.014. Epub 2021 Feb 24.
Ref 147	m(6) A modification of lncRNA PCAT6 promotes bone metastasis in prostate cancer through IGF2BP2-mediated IGF1R mRNA stabilization. Clin Transl Med. 2021 Jun;11(6):e426. doi: 10.1002/ctm2.426.
Ref 148	Comprehensive Pan-Cancer Analysis of the Prognostic and Immunological Roles of the METTL3/lncRNA-SNHG1/miRNA-140-3p/UBE2C Axis. Front Cell Dev Biol. 2021 Nov 10;9:765772. doi: 10.3389/fcell.2021.765772. eCollection 2021.
Ref 149	lncRNA THAP7-AS1, transcriptionally activated by SP1 and post-transcriptionally stabilized by METTL3-mediated m6A modification, exerts oncogenic properties by improving CUL4B entry into the nucleus. Cell Death Differ. 2022 Mar;29(3):627-641. doi: 10.1038/s41418-021-00879-9. Epub 2021 Oct 4.
Ref 150	METTL3-Mediated ADAMTS9 Suppression Facilitates Angiogenesis and Carcinogenesis in Gastric Cancer. Front Oncol. 2022 Apr 28;12:861807. doi: 10.3389/fonc.2022.861807. eCollection 2022.
Ref 151	Dysregulated N6-methyladenosine?methylation writer METTL3 contributes to the proliferation and migration of gastric cancer. J Cell Physiol. 2020 Jan;235(1):548-562. doi: 10.1002/jcp.28994. Epub 2019 Jun 24.
Ref 152	Adenylate Kinase 4 Modulates the Resistance of Breast Cancer Cells to Tamoxifen through an m(6)A-Based Epitranscriptomic Mechanism. Mol Ther. 2020 Dec 2;28(12):2593-2604. doi: 10.1016/j.ymthe.2020.09.007. Epub 2020 Sep 5.
Ref 153	The essential roles of m(6)A RNA modification to stimulate ENO1-dependent glycolysis and tumorigenesis in lung adenocarcinoma. J Exp Clin Cancer Res. 2022 Jan 25;41(1):36. doi: 10.1186/s13046-021-02200-5.
Ref 154	Vitamin D3 Suppresses Human Cytomegalovirus-Induced Vascular Endothelial Apoptosis via Rectification of Paradoxical m6A Modification of Mitochondrial Calcium Uniporter mRNA, Which Is Regulated by METTL3 and YTHDF3. Front Microbiol. 2022 Mar 11;13:861734. doi: 10.3389/fmicb.2022.861734. eCollection 2022.
Ref 155	METTL3-m(6)A-Rubicon axis inhibits autophagy in nonalcoholic fatty liver disease. Mol Ther. 2022 Feb 2;30(2):932-946. doi: 10.1016/j.ymthe.2021.09.016. Epub 2021 Sep 20.
Ref 156	METTL3 Regulates Liver Homeostasis, Hepatocyte Ploidy, and Circadian Rhythm-Controlled Gene Expression in Mice. Am J Pathol. 2022 Jan;192(1):56-71. doi: 10.1016/j.ajpath.2021.09.005. Epub 2021 Sep 29.
Ref 157	CircMETTL3, upregulated in a m6A-dependent manner, promotes breast cancer progression. Int J Biol Sci. 2021 Mar 15;17(5):1178-1190. doi: 10.7150/ijbs.57783. eCollection 2021.
Ref 158	The N6-methyladenosine modification enhances ferroptosis resistance through inhibiting SLC7A11 mRNA deadenylation in hepatoblastoma. Clin Transl Med. 2022 May;12(5):e778. doi: 10.1002/ctm2.778.
Ref 159	METTL3 promotes lung adenocarcinoma tumor growth and inhibits ferroptosis by stabilizing SLC7A11 m(6)A modification. Cancer Cell Int. 2022 Jan 7;22(1):11. doi: 10.1186/s12935-021-02433-6.
Ref 160	The aberrant cross-talk of epithelium-macrophages via METTL3-regulated extracellular vesicle miR-93 in smoking-induced emphysema. Cell Biol Toxicol. 2022 Feb;38(1):167-183. doi: 10.1007/s10565-021-09585-1. Epub 2021 Mar 4.
Ref 161	METTL3-mediated N6-methyladenosine modification of DUSP5 mRNA promotes gallbladder-cancer progression. Cancer Gene Ther. 2022 Jul;29(7):1012-1020. doi: 10.1038/s41417-021-00406-5. Epub 2021 Nov 19.
Ref 162	METTL3 Regulates Osteoblast Differentiation and Inflammatory Response via Smad Signaling and MAPK Signaling. Int J Mol Sci. 2019 Dec 27;21(1):199. doi: 10.3390/ijms21010199.
Ref 163	Silencing of METTL3 effectively hinders invasion and metastasis of prostate cancer cells. Theranostics. 2021 Jun 11;11(16):7640-7657. doi: 10.7150/thno.61178. eCollection 2021.
Ref 164	METTL3 induces PLX4032 resistance in melanoma by promoting m(6)A-dependent EGFR translation. Cancer Lett. 2021 Dec 1;522:44-56. doi: 10.1016/j.canlet.2021.09.015. Epub 2021 Sep 13.
Ref 165	METTL3-mediated m(6)A mRNA modification of FBXW7 suppresses lung adenocarcinoma. J Exp Clin Cancer Res. 2021 Mar 6;40(1):90. doi: 10.1186/s13046-021-01880-3.
Ref 166	Circular RNA circNRIP1 plays oncogenic roles in the progression of osteosarcoma. Mamm Genome. 2021 Dec;32(6):448-456. doi: 10.1007/s00335-021-09891-3. Epub 2021 Jul 10.
Ref 167	RNA m(6) A methylation regulates sorafenib resistance in liver cancer through FOXO3-mediated autophagy. EMBO J. 2020 Jun 17;39(12):e103181. doi: 10.15252/embj.2019103181. Epub 2020 May 5.
Ref 168	METTL3 serves an oncogenic role in human ovarian cancer cells partially via the AKT signaling pathway. Oncol Lett. 2020 Apr;19(4):3197-3204. doi: 10.3892/ol.2020.11425. Epub 2020 Mar 3.
Ref 169	N(6)-Methyladenosine Associated Silencing of miR-193b Promotes Cervical Cancer Aggressiveness by Targeting CCND1. Front Oncol. 2021 Jun 10;11:666597. doi: 10.3389/fonc.2021.666597. eCollection 2021.
Ref 170	ZFP217 regulates adipogenesis by controlling mitotic clonal expansion in a METTL3-m(6)A dependent manner. RNA Biol. 2019 Dec;16(12):1785-1793. doi: 10.1080/15476286.2019.1658508. Epub 2019 Aug 27.
Ref 171	RNA N(6)-Methyladenosine Methyltransferase METTL3 Facilitates Colorectal Cancer by Activating the m(6)A-GLUT1-mTORC1 Axis and Is a Therapeutic Target. Gastroenterology. 2021 Mar;160(4):1284-1300.e16. doi: 10.1053/j.gastro.2020.11.013. Epub 2020 Nov 18.
Ref 172	Integrated analysis of the transcriptome-wide m6A methylome in preeclampsia and healthy control placentas. PeerJ. 2020 Sep 15;8:e9880. doi: 10.7717/peerj.9880. eCollection 2020.
Ref 173	Chidamide increases the sensitivity of Non-small Cell Lung Cancer to Crizotinib by decreasing c-MET mRNA methylation. Int J Biol Sci. 2020 Jul 19;16(14):2595-2611. doi: 10.7150/ijbs.45886. eCollection 2020.
Ref 174	RNA methyltransferase METTL3 induces intrinsic resistance to gefitinib by combining with MET to regulate PI3K/AKT pathway in lung adenocarcinoma. J Cell Mol Med. 2021 Mar;25(5):2418-2425. doi: 10.1111/jcmm.16114. Epub 2021 Jan 24.
Ref 175	RNA m(6) A methylation regulates uveal melanoma cell proliferation, migration, and invasion by targeting c-Met. J Cell Physiol. 2020 Oct;235(10):7107-7119. doi: 10.1002/jcp.29608. Epub 2020 Feb 4.
Ref 176	LINC00460/DHX9/IGF2BP2 complex promotes colorectal cancer proliferation and metastasis by mediating HMGA1 mRNA stability depending on m6A modification. J Exp Clin Cancer Res. 2021 Feb 1;40(1):52. doi: 10.1186/s13046-021-01857-2.
Ref 177	METTL3 stabilizes HDAC5 mRNA in an m(6)A-dependent manner to facilitate malignant proliferation of osteosarcoma cells. Cell Death Discov. 2022 Apr 8;8(1):179. doi: 10.1038/s41420-022-00926-5.
Ref 178	METTL3/YTHDF2 m(6) A axis promotes tumorigenesis by degrading SETD7 and KLF4 mRNAs in bladder cancer. J Cell Mol Med. 2020 Apr;24(7):4092-4104. doi: 10.1111/jcmm.15063. Epub 2020 Mar 3.
Ref 179	MicroRNA-135 inhibits initiation of epithelial-mesenchymal transition in breast cancer by targeting ZNF217 and promoting m6A modification of NANOG. Oncogene. 2022 Mar;41(12):1742-1751. doi: 10.1038/s41388-022-02211-2. Epub 2022 Feb 4.
Ref 180	HBXIP drives metabolic reprogramming in hepatocellular carcinoma cells via METTL3-mediated m6A modification of HIF-1Alpha. J Cell Physiol. 2021 May;236(5):3863-3880. doi: 10.1002/jcp.30128. Epub 2020 Dec 11.
Ref 181	N(6)-methyladenosine modification of ITGA6 mRNA promotes the development and progression of bladder cancer. EBioMedicine. 2019 Sep;47:195-207. doi: 10.1016/j.ebiom.2019.07.068. Epub 2019 Aug 10.
Ref 182	METTL3 enhances cell adhesion through stabilizing integrin Beta1 mRNA via an m6A-HuR-dependent mechanism in prostatic carcinoma. Am J Cancer Res. 2020 Mar 1;10(3):1012-1025. eCollection 2020.
Ref 183	N(6)-Methyladenosine METTL3 Modulates the Proliferation and Apoptosis of Lens Epithelial Cells in Diabetic Cataract. Mol Ther Nucleic Acids. 2020 Jun 5;20:111-116. doi: 10.1016/j.omtn.2020.02.002. Epub 2020 Feb 11.
Ref 184	METTL3 promotes intrahepatic cholangiocarcinoma progression by regulating IFIT2 expression in an m(6)A-YTHDF2-dependent manner. Oncogene. 2022 Mar;41(11):1622-1633. doi: 10.1038/s41388-022-02185-1. Epub 2022 Jan 29.
Ref 185	ADAR1 is a new target of METTL3 and plays a pro-oncogenic role in glioblastoma by an editing-independent mechanism. Genome Biol. 2021 Jan 28;22(1):51. doi: 10.1186/s13059-021-02271-9.
Ref 186	Long non-coding RNA ILF3-AS1 facilitates hepatocellular carcinoma progression by stabilizing ILF3 mRNA in an m(6)A-dependent manner. Hum Cell. 2021 Nov;34(6):1843-1854. doi: 10.1007/s13577-021-00608-x. Epub 2021 Sep 7.
Ref 187	METTL3 Promotes Activation and Inflammation of FLSs Through the NF-KappaB Signaling Pathway in Rheumatoid Arthritis. Front Med (Lausanne). 2021 Jul 6;8:607585. doi: 10.3389/fmed.2021.607585. eCollection 2021.
Ref 188	METTL3-mediated mRNA N(6)-methyladenosine is required for oocyte and follicle development in mice. Cell Death Dis. 2021 Oct 23;12(11):989. doi: 10.1038/s41419-021-04272-9.
Ref 189	METTL3-mediated m6A modification of KIF3C-mRNA promotes prostate cancer progression and is negatively regulated by miR-320d. Aging (Albany NY). 2021 Sep 19;13(18):22332-22344. doi: 10.18632/aging.203541. Epub 2021 Sep 19.
Ref 190	METTL3-mediated m(6)A methylation of SPHK2 promotes gastric cancer progression by targeting KLF2. Oncogene. 2021 Apr;40(16):2968-2981. doi: 10.1038/s41388-021-01753-1. Epub 2021 Mar 23.
Ref 191	The m6A methyltransferase METTL3 promotes osteosarcoma progression by regulating the m6A level of LEF1. Biochem Biophys Res Commun. 2019 Aug 27;516(3):719-725. doi: 10.1016/j.bbrc.2019.06.128. Epub 2019 Jun 26.
Ref 192	m6A methyltransferase METTL3 promotes the progression of prostate cancer via m6A-modified LEF1. Eur Rev Med Pharmacol Sci. 2020 Apr;24(7):3565-3571. doi: 10.26355/eurrev_202004_20817.
Ref 193	METTL3 modulates m6A modification of CDC25B and promotes head and neck squamous cell carcinoma malignant progression. Exp Hematol Oncol. 2022 Mar 14;11(1):14. doi: 10.1186/s40164-022-00256-3.
Ref 194	m(6)A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells. Cell Rep. 2017 Mar 14;18(11):2622-2634. doi: 10.1016/j.celrep.2017.02.059.
Ref 195	METTL3-mediated m6A modification of STEAP2 mRNA inhibits papillary thyroid cancer progress by blocking the Hedgehog signaling pathway and epithelial-to-mesenchymal transition. Cell Death Dis. 2022 Apr 18;13(4):358. doi: 10.1038/s41419-022-04817-6.
Ref 196	METTL3 promotes prostate cancer progression by regulating miR-182 maturation in m6A-dependent manner. Andrologia. 2022 Aug;54(7):1581-1591. doi: 10.1111/and.14422. Epub 2022 Apr 12.
Ref 197	Exosomal and intracellular miR-320b promotes lymphatic metastasis in esophageal squamous cell carcinoma. Mol Ther Oncolytics. 2021 Sep 25;23:163-180. doi: 10.1016/j.omto.2021.09.003. eCollection 2021 Dec 17.
Ref 198	METTL3 promotes IL-1Beta-induced degeneration of endplate chondrocytes by driving m6A-dependent maturation of miR-126-5p. J Cell Mol Med. 2020 Dec;24(23):14013-14025. doi: 10.1111/jcmm.16012. Epub 2020 Oct 23.
Ref 199	N(6)-methyladenosine (m(6)A) methyltransferase METTL3-mediated LINC00680 accelerates osteoarthritis through m(6)A/SIRT1 manner. Cell Death Discov. 2022 May 2;8(1):240. doi: 10.1038/s41420-022-00890-0.
Ref 200	METTL3-mediated m(6)A mRNA modification promotes esophageal cancer initiation and progression via Notch signaling pathway. Mol Ther Nucleic Acids. 2021 Jul 21;26:333-346. doi: 10.1016/j.omtn.2021.07.007. eCollection 2021 Dec 3.
Ref 201	Therapeutic targeting m6A-guided miR-146a-5p signaling contributes to the melittin-induced selective suppression of bladder cancer. Cancer Lett. 2022 May 28;534:215615. doi: 10.1016/j.canlet.2022.215615. Epub 2022 Mar 9.
Ref 202	YTHDF2 facilitates UBXN1 mRNA decay by recognizing METTL3-mediated m(6)A modification to activate NF-KappaB and promote the malignant progression of glioma. J Hematol Oncol. 2021 Jul 10;14(1):109. doi: 10.1186/s13045-021-01124-z.
Ref 203	METTL3/METTL14 Transactivation and m(6)A-Dependent TGF-Beta1 Translation in Activated Kupffer Cells. Cell Mol Gastroenterol Hepatol. 2021;12(3):839-856. doi: 10.1016/j.jcmgh.2021.05.007. Epub 2021 May 13.
Ref 204	NUCB1 Suppresses Growth and Shows Additive Effects With Gemcitabine in Pancreatic Ductal Adenocarcinoma via the Unfolded Protein Response. Front Cell Dev Biol. 2021 Mar 29;9:641836. doi: 10.3389/fcell.2021.641836. eCollection 2021.
Ref 205	Methyltransferase-Like 3 Rescues the Amyloid-beta protein-Induced Reduction of Activity-Regulated Cytoskeleton Associated Protein Expression via YTHDF1-Dependent N6-Methyladenosine Modification. Front Aging Neurosci. 2022 Apr 25;14:890134. doi: 10.3389/fnagi.2022.890134. eCollection 2022.
Ref 206	METTL3 regulates PM(2.5)-induced cell injury by targeting OSGIN1 in human airway epithelial cells. J Hazard Mater. 2021 Aug 5;415:125573. doi: 10.1016/j.jhazmat.2021.125573. Epub 2021 Mar 3.
Ref 207	miR-600 inhibits lung cancer via downregulating the expression of METTL3. Cancer Manag Res. 2019 Feb 1;11:1177-1187. doi: 10.2147/CMAR.S181058. eCollection 2019.
Ref 208	METTL3 promotes oxaliplatin resistance of gastric cancer CD133+?stem cells by promoting PARP1 mRNA stability. Cell Mol Life Sci. 2022 Feb 18;79(3):135. doi: 10.1007/s00018-022-04129-0.
Ref 209	METTL3 Promotes Tumorigenesis and Metastasis through BMI1 m(6)A Methylation in Oral Squamous Cell Carcinoma. Mol Ther. 2020 Oct 7;28(10):2177-2190. doi: 10.1016/j.ymthe.2020.06.024. Epub 2020 Jun 24.
Ref 210	METTL3/YTHDF2 m6A axis accelerates colorectal carcinogenesis through epigenetically suppressing YPEL5. Mol Oncol. 2021 Aug;15(8):2172-2184. doi: 10.1002/1878-0261.12898. Epub 2021 Jan 25.
Ref 211	METTL3 mediates bone marrow mesenchymal stem cell adipogenesis to promote chemoresistance in acute myeloid leukaemia. FEBS Open Bio. 2021 Jun;11(6):1659-1672. doi: 10.1002/2211-5463.13165. Epub 2021 May 20.
Ref 212	METTL3 promotes the proliferation and invasion of esophageal cancer cells partly through AKT signaling pathway. Pathol Res Pract. 2020 Sep;216(9):153087. doi: 10.1016/j.prp.2020.153087. Epub 2020 Jun 27.
Ref 213	Methyltransferase-like 3 upregulation is involved in the chemoresistance of non-small cell lung cancer. Ann Transl Med. 2022 Feb;10(3):139. doi: 10.21037/atm-21-6608.
Ref 214	HBXIP-elevated methyltransferase METTL3 promotes the progression of breast cancer via inhibiting tumor suppressor let-7g. Cancer Lett. 2018 Feb 28;415:11-19. doi: 10.1016/j.canlet.2017.11.018. Epub 2017 Nov 22.
Ref 215	Impaired autophagic degradation of lncRNA ARHGAP5-AS1 promotes chemoresistance in gastric cancer. Cell Death Dis. 2019 May 16;10(6):383. doi: 10.1038/s41419-019-1585-2.
Ref 216	N6-methyladenosine regulates ATM expression and downstream signaling. J Cancer. 2021 Oct 17;12(23):7041-7051. doi: 10.7150/jca.64061. eCollection 2021.
Ref 217	N(6)-Methyladenosine Modulates Nonsense-Mediated mRNA Decay in Human Glioblastoma. Cancer Res. 2019 Nov 15;79(22):5785-5798. doi: 10.1158/0008-5472.CAN-18-2868. Epub 2019 Sep 17.
Ref 218	METTL3-mediated m(6)A modification regulates cell cycle progression of dental pulp stem cells. Stem Cell Res Ther. 2021 Mar 1;12(1):159. doi: 10.1186/s13287-021-02223-x.
Ref 219	LINC01605, regulated by the EP300-SMYD2 complex, potentiates the binding between METTL3 and SPTBN2 in colorectal cancer. Cancer Cell Int. 2021 Sep 20;21(1):504. doi: 10.1186/s12935-021-02180-8.
Ref 220	Upregulated METTL3 promotes metastasis of colorectal Cancer via miR-1246/SPRED2/MAPK signaling pathway. J Exp Clin Cancer Res. 2019 Sep 6;38(1):393. doi: 10.1186/s13046-019-1408-4.
Ref 221	Histone demethylase JMJD1C promotes the polarization of M1 macrophages to prevent glioma by upregulating miR-302a. Clin Transl Med. 2021 Sep;11(9):e424. doi: 10.1002/ctm2.424.
Ref 222	Knockdown of m6A methyltransferase METTL3 in gastric cancer cells results in suppression of cell proliferation. Oncol Lett. 2020 Sep;20(3):2191-2198. doi: 10.3892/ol.2020.11794. Epub 2020 Jul 1.
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Ref 225	METTL3 Is Involved in the Development of Graves' Disease by Inducing SOCS mRNA m6A Modification. Front Endocrinol (Lausanne). 2021 Sep 20;12:666393. doi: 10.3389/fendo.2021.666393. eCollection 2021.
Ref 226	m(6)A Methyltransferase METTL3 Promotes the Progression of Primary Acral Melanoma via Mediating TXNDC5 Methylation. Front Oncol. 2022 Jan 18;11:770325. doi: 10.3389/fonc.2021.770325. eCollection 2021.
Ref 227	Promoter-bound METTL3 maintains myeloid leukaemia by m(6)A-dependent translation control. Nature. 2017 Dec 7;552(7683):126-131. doi: 10.1038/nature24678. Epub 2017 Nov 27.
Ref 228	METTL3 facilitates multiple myeloma tumorigenesis by enhancing YY1 stability and pri-microRNA-27 maturation in m(6)A-dependent manner. Cell Biol Toxicol. 2022 Jan 17. doi: 10.1007/s10565-021-09690-1. Online ahead of print.
Ref 229	METTL3 promotes ovarian carcinoma growth and invasion through the regulation of AXL translation and epithelial to mesenchymal transition. Gynecol Oncol. 2018 Nov;151(2):356-365. doi: 10.1016/j.ygyno.2018.09.015. Epub 2018 Sep 21.
Ref 230	METTL3 facilitates the progression of hepatocellular carcinoma by modulating the m6A level of USP7. Am J Transl Res. 2021 Dec 15;13(12):13423-13437. eCollection 2021.
Ref 231	Methyltransferase-like 3 Aggravates HCC Development via Mediating N6-Methyladenosine of Ubiquitin-Specific Protease 7. J Oncol. 2022 May 5;2022:6167832. doi: 10.1155/2022/6167832. eCollection 2022.
Ref 232	METTL3-induced UCK2 m(6)A hypermethylation promotes melanoma cancer cell metastasis via the WNT/Beta-catenin pathway. Ann Transl Med. 2021 Jul;9(14):1155. doi: 10.21037/atm-21-2906.
Ref 233	METTL3 promotes colorectal cancer metastasis by stabilizing PLAU mRNA in an m6A-dependent manner. Biochem Biophys Res Commun. 2022 Jul 23;614:9-16. doi: 10.1016/j.bbrc.2022.04.141. Epub 2022 May 6.
Ref 234	Mettl3 Regulates Osteogenic Differentiation and Alternative Splicing of Vegfa in Bone Marrow Mesenchymal Stem Cells. Int J Mol Sci. 2019 Jan 28;20(3):551. doi: 10.3390/ijms20030551.
Ref 235	N6-Methyladenosine Regulates the Expression and Secretion of TGFBeta1 to Affect the Epithelial-Mesenchymal Transition of Cancer Cells. Cells. 2020 Jan 25;9(2):296. doi: 10.3390/cells9020296.
Ref 236	The m6A methyltransferase METTL3 aggravates the progression of nasopharyngeal carcinoma through inducing EMT by m6A-modified Snail mRNA. Minerva Med. 2022 Apr;113(2):309-314. doi: 10.23736/S0026-4806.20.06653-7. Epub 2020 Jun 5.
Ref 237	RNA m(6)A methyltransferase METTL3 promotes colorectal cancer cell proliferation and invasion by regulating Snail expression. Oncol Lett. 2021 Oct;22(4):711. doi: 10.3892/ol.2021.12972. Epub 2021 Aug 5.
Ref 238	RNA m(6)A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail. Nat Commun. 2019 May 6;10(1):2065. doi: 10.1038/s41467-019-09865-9.
Ref 239	SUMO1 modification of methyltransferase-like 3 promotes tumor progression via regulating Snail mRNA homeostasis in hepatocellular carcinoma. Theranostics. 2020 Apr 27;10(13):5671-5686. doi: 10.7150/thno.42539. eCollection 2020.
Ref 240	N6-methyladenosine methyltransferase plays a role in hypoxic preconditioning partially through the interaction with lncRNA H19. Acta Biochim Biophys Sin (Shanghai). 2020 Dec 29;52(12):1306-1315. doi: 10.1093/abbs/gmaa130.
Ref 241	LncRNA LINC00470 promotes the degradation of PTEN mRNA to facilitate malignant behavior in gastric cancer cells. Biochem Biophys Res Commun. 2020 Jan 22;521(4):887-893. doi: 10.1016/j.bbrc.2019.11.016. Epub 2019 Nov 8.
Ref 242	m(6)A Modification of lncRNA NEAT1 Regulates Chronic Myelocytic Leukemia Progression via miR-766-5p/CDKN1A Axis. Front Oncol. 2021 Jul 20;11:679634. doi: 10.3389/fonc.2021.679634. eCollection 2021.
Ref 243	Cross talk between RNA N6-methyladenosine methyltransferase-like 3 and miR-186 regulates hepatoblastoma progression through Wnt/Beta-catenin signalling pathway. Cell Prolif. 2020 Mar;53(3):e12768. doi: 10.1111/cpr.12768. Epub 2020 Jan 22.
Ref 244	METTL3 promote tumor proliferation of bladder cancer by accelerating pri-miR221/222 maturation in m6A-dependent manner. Mol Cancer. 2019 Jun 22;18(1):110. doi: 10.1186/s12943-019-1036-9.
Ref 245	Methyltransferase 3 Mediated miRNA m6A Methylation Promotes Stress Granule Formation in the Early Stage of Acute Ischemic Stroke. Front Mol Neurosci. 2020 Jun 5;13:103. doi: 10.3389/fnmol.2020.00103. eCollection 2020.
Ref 246	Extracellular vesicle-packaged mitochondrial disturbing miRNA exacerbates cardiac injury during acute myocardial infarction. Clin Transl Med. 2022 Apr;12(4):e779. doi: 10.1002/ctm2.779.
Ref 247	The "m6A writer" METTL3 and the "m6A reader" IGF2BP2 regulate cutaneous T-cell lymphomas progression via CDKN2A. Hematol Oncol. 2022 Apr 21. doi: 10.1002/hon.3005. Online ahead of print.
Ref 248	Methylation of adenosine at the N(6) position post-transcriptionally regulates hepatic P450s expression. Biochem Pharmacol. 2020 Jan;171:113697. doi: 10.1016/j.bcp.2019.113697. Epub 2019 Nov 7.
Ref 249	METTL3 Promotes Esophageal Squamous Cell Carcinoma Metastasis Through Enhancing GLS2 Expression. Front Oncol. 2021 May 19;11:667451. doi: 10.3389/fonc.2021.667451. eCollection 2021.
Ref 250	The methyltransferase METTL3 negatively regulates nonalcoholic steatohepatitis (NASH) progression. Nat Commun. 2021 Dec 10;12(1):7213. doi: 10.1038/s41467-021-27539-3.
Ref 251	N(6)-methyladenosine modification regulates imatinib resistance of gastrointestinal stromal tumor by enhancing the expression of multidrug transporter MRP1. Cancer Lett. 2022 Apr 1;530:85-99. doi: 10.1016/j.canlet.2022.01.008. Epub 2022 Jan 13.
Ref 252	Mechanism of METTL3-Mediated m(6)A Modification in Cardiomyocyte Pyroptosis and Myocardial Ischemia-Reperfusion Injury. Cardiovasc Drugs Ther. 2022 Jan 23. doi: 10.1007/s10557-021-07300-0. Online ahead of print.
Ref 253	METTL3 Contributes to Osteosarcoma Progression by Increasing DANCR mRNA Stability via m6A Modification. Front Cell Dev Biol. 2022 Jan 12;9:784719. doi: 10.3389/fcell.2021.784719. eCollection 2021.
Ref 254	m(6) A transferase METTL3-induced lncRNA ABHD11-AS1 promotes the Warburg effect of non-small-cell lung cancer. J Cell Physiol. 2021 Apr;236(4):2649-2658. doi: 10.1002/jcp.30023. Epub 2020 Sep 6.
Ref 255	N(6)-methyladenosine-modified long non-coding RNA AGAP2-AS1 promotes psoriasis pathogenesis via miR-424-5p/AKT3 axis. J Dermatol Sci. 2022 Jan;105(1):27-36. doi: 10.1016/j.jdermsci.2021.11.007. Epub 2021 Nov 18.
Ref 256	Long intergenic non-protein coding RNA 1273 confers sorafenib resistance in hepatocellular carcinoma via regulation of methyltransferase 3. Bioengineered. 2022 Feb;13(2):3108-3121. doi: 10.1080/21655979.2022.2025701.
Ref 257	m6A-Induced LncRNA MEG3 Suppresses the Proliferation, Migration and Invasion of Hepatocellular Carcinoma Cell Through miR-544b/BTG2 Signaling. Onco Targets Ther. 2021 Jun 15;14:3745-3755. doi: 10.2147/OTT.S289198. eCollection 2021.
Ref 258	Upregulation of lncRNA NIFK-AS1 in hepatocellular carcinoma by m(6)A methylation promotes disease progression and sorafenib resistance. Hum Cell. 2021 Nov;34(6):1800-1811. doi: 10.1007/s13577-021-00587-z. Epub 2021 Aug 10.
Ref 259	Targeting SNHG3/miR-186-5p reverses the increased m6A level caused by platinum treatment through regulating METTL3 in esophageal cancer. Cancer Cell Int. 2021 Feb 17;21(1):114. doi: 10.1186/s12935-021-01747-9.
Ref 260	N6-methyladenosine-induced SVIL antisense RNA 1 restrains lung adenocarcinoma cell proliferation by destabilizing E2F1. Bioengineered. 2022 Feb;13(2):3093-3107. doi: 10.1080/21655979.2022.2025697.
Ref 261	METTL3 Regulates Ossification of the Posterior Longitudinal Ligament via the lncRNA XIST/miR-302a-3p/USP8 Axis. Front Cell Dev Biol. 2021 Mar 5;9:629895. doi: 10.3389/fcell.2021.629895. eCollection 2021.
Ref 262	The m6A methyltransferase METTL3 affects autophagy and progression of nasopharyngeal carcinoma by regulating the stability of lncRNA ZFAS1. Infect Agent Cancer. 2022 Jan 3;17(1):1. doi: 10.1186/s13027-021-00411-1.
Ref 263	ZFAS1 Exerts an Oncogenic Role via Suppressing miR-647 in an m(6)A-Dependent Manner in Cervical Cancer. Onco Targets Ther. 2020 Nov 17;13:11795-11806. doi: 10.2147/OTT.S274492. eCollection 2020.
Ref 264	Methyltransferase-like 3 induces the development of cervical cancer by enhancing insulin-like growth factor 2 mRNA-binding proteins 3-mediated apoptotic chromatin condensation inducer 1 mRNA stability. Bioengineered. 2022 Mar;13(3):7034-7048. doi: 10.1080/21655979.2022.2044261.
Ref 265	METTL3 Inhibits Antitumor Immunity by Targeting m(6)A-BHLHE41-CXCL1/CXCR2 Axis to Promote Colorectal Cancer. Gastroenterology. 2022 Jun 11:S0016-5085(22)00629-1. doi: 10.1053/j.gastro.2022.06.024. Online ahead of print.
Ref 266	METTL3-mediated RNA m6A Hypermethylation Promotes Tumorigenesis and GH Secretion of Pituitary Somatotroph Adenomas. J Clin Endocrinol Metab. 2022 Jan 1;107(1):136-149. doi: 10.1210/clinem/dgab652.
Ref 267	N(6)-methyladenosine-mediated LDHA induction potentiates chemoresistance of colorectal cancer cells through metabolic reprogramming. Theranostics. 2022 Jun 13;12(10):4802-4817. doi: 10.7150/thno.73746. eCollection 2022.
Ref 268	Targeting m6A modification inhibits herpes virus 1 infection. Genes Dis. 2021 Feb 22;9(4):1114-1128. doi: 10.1016/j.gendis.2021.02.004. eCollection 2022 Jul.
Ref 269	N6-methyladenosine methyltransferase METTL3 affects the phenotype of cerebral arteriovenous malformation via modulating Notch signaling pathway. J Biomed Sci. 2020 May 9;27(1):62. doi: 10.1186/s12929-020-00655-w.
Ref 270	Role of METTL3-Dependent N(6)-Methyladenosine mRNA Modification in the Promotion of Angiogenesis. Mol Ther. 2020 Oct 7;28(10):2191-2202. doi: 10.1016/j.ymthe.2020.07.022. Epub 2020 Jul 25.
Ref 271	METTL3 promotes colorectal carcinoma progression by regulating the m6A-CRB3-Hippo axis. J Exp Clin Cancer Res. 2022 Jan 10;41(1):19. doi: 10.1186/s13046-021-02227-8.
Ref 272	N6-Methyladenosine Modification of PTTG3P Contributes to Colorectal Cancer Proliferation via YAP1. Front Oncol. 2021 Sep 30;11:669731. doi: 10.3389/fonc.2021.669731. eCollection 2021.
Ref 273	METTL3 antagonizes 5?FU chemotherapy and confers drug resistance in colorectal carcinoma. Int J Oncol. 2022 Sep;61(3):106. doi: 10.3892/ijo.2022.5396. Epub 2022 Jul 20.
Ref 274	Increased m(6)A modification of lncRNA DBH-AS1 suppresses pancreatic cancer growth and gemcitabine resistance via the miR-3163/USP44 axis. Ann Transl Med. 2022 Mar;10(6):304. doi: 10.21037/atm-22-556.
Ref 275	M(6)A-mediated up-regulation of LncRNA LIFR-AS1 enhances the progression of pancreatic cancer via miRNA-150-5p/ VEGFA/Akt signaling. Cell Cycle. 2021 Dec;20(23):2507-2518. doi: 10.1080/15384101.2021.1991122. Epub 2021 Oct 17.
Ref 276	The functions of N6-methyladenosine modification in lncRNAs. Genes Dis. 2020 Mar 19;7(4):598-605. doi: 10.1016/j.gendis.2020.03.005. eCollection 2020 Dec.
Ref 277	METTL3-stabilized lncRNA SNHG7 accelerates glycolysis in prostate cancer via SRSF1/c-Myc axis. Exp Cell Res. 2022 Jul 1;416(1):113149. doi: 10.1016/j.yexcr.2022.113149. Epub 2022 Apr 9.
Ref 278	Inhibition of METTL3/m6A/miR126 promotes the migration and invasion of endometrial stromal cells in endometriosis?. Biol Reprod. 2021 Nov 15;105(5):1221-1233. doi: 10.1093/biolre/ioab152.
Ref 279	N(6) -methyladenosine modification of circular RNA circ-ARL3 facilitates Hepatitis B virus-associated hepatocellular carcinoma via sponging miR-1305. IUBMB Life. 2021 Feb;73(2):408-417. doi: 10.1002/iub.2438. Epub 2020 Dec 28.
Ref 280	METTL3 suppresses neuropathic pain via modulating N6-methyladenosine-dependent primary miR-150 processing. Cell Death Discov. 2022 Feb 24;8(1):80. doi: 10.1038/s41420-022-00880-2.
Ref 281	Excessive miR-25-3p maturation via N(6)-methyladenosine stimulated by cigarette smoke promotes pancreatic cancer progression. Nat Commun. 2019 Apr 23;10(1):1858. doi: 10.1038/s41467-019-09712-x.
Ref 282	Stimulation of Let-7 Maturation by Metformin Improved the Response to Tyrosine Kinase Inhibitor Therapy in an m6A Dependent Manner. Front Oncol. 2022 Jan 6;11:731561. doi: 10.3389/fonc.2021.731561. eCollection 2021.
Ref 283	METTL3-mediated maturation of miR-126-5p promotes ovarian cancer progression via PTEN-mediated PI3K/Akt/mTOR pathway. Cancer Gene Ther. 2021 Apr;28(3-4):335-349. doi: 10.1038/s41417-020-00222-3. Epub 2020 Sep 16.
Ref 284	N6-methyladenosine induced miR-143-3p promotes the brain metastasis of lung cancer via regulation of VASH1. Mol Cancer. 2019 Dec 10;18(1):181. doi: 10.1186/s12943-019-1108-x.
Ref 285	METTL3/N6-methyladenosine/ miR-21-5p promotes obstructive renal fibrosis by regulating inflammation through SPRY1/ERK/NF-KappaB pathway activation. J Cell Mol Med. 2021 Aug;25(16):7660-7674. doi: 10.1111/jcmm.16603. Epub 2021 Jun 24.
Ref 286	Overexpression of METTL3 attenuates high-glucose induced RPE cell pyroptosis by regulating miR-25-3p/PTEN/Akt signaling cascade through DGCR8. Aging (Albany NY). 2020 May 4;12(9):8137-8150. doi: 10.18632/aging.103130. Epub 2020 May 4.
Ref 287	MiR-29a-3p Improves Acute Lung Injury by Reducing Alveolar Epithelial Cell PANoptosis. Aging Dis. 2022 Jun 1;13(3):899-909. doi: 10.14336/AD.2021.1023. eCollection 2022 Jun.
Ref 288	METTL3 Induces AAA Development and Progression by Modulating N6-Methyladenosine-Dependent Primary miR34a Processing. Mol Ther Nucleic Acids. 2020 Sep 4;21:394-411. doi: 10.1016/j.omtn.2020.06.005. Epub 2020 Jun 10.
Ref 289	Silencing METTL3 Stabilizes Atherosclerotic Plaques by Regulating the Phenotypic Transformation of Vascular Smooth Muscle Cells via the miR-375-3p/PDK1 Axis. Cardiovasc Drugs Ther. 2022 Jun 15. doi: 10.1007/s10557-022-07348-6. Online ahead of print.
Ref 290	N(6)-methyladenosine-mediated miR-380-3p maturation and upregulation promotes cancer aggressiveness in pancreatic cancer. Bioengineered. 2022 Jun;13(6):14460-14471. doi: 10.1080/21655979.2022.2088497.
Ref 291	Oxygen glucose deprivation/re-oxygenation-induced neuronal cell death is associated with Lnc-D63785 m6A methylation and miR-422a accumulation. Cell Death Dis. 2020 Sep 30;11(9):816. doi: 10.1038/s41419-020-03021-8.
Ref 292	m(5) C and m(6) A modification of long noncoding NKILA accelerates cholangiocarcinoma progression via the miR-582-3p-YAP1 axis. Liver Int. 2022 May;42(5):1144-1157. doi: 10.1111/liv.15240. Epub 2022 Mar 21.
Ref 293	METTL3-mediated maturation of miR-589-5p promotes the malignant development of liver cancer. J Cell Mol Med. 2022 May;26(9):2505-2519. doi: 10.1111/jcmm.16845. Epub 2022 Mar 29.
Ref 294	METTL3/m(6)A/miRNA-873-5p Attenuated Oxidative Stress and Apoptosis in Colistin-Induced Kidney Injury by Modulating Keap1/Nrf2 Pathway. Front Pharmacol. 2019 May 15;10:517. doi: 10.3389/fphar.2019.00517. eCollection 2019.
Ref 295	SUMOylation of methyltransferase-like 3 facilitates colorectal cancer progression by promoting circ_0000677 in an m(6) A-dependent manner. J Gastroenterol Hepatol. 2022 Apr;37(4):700-713. doi: 10.1111/jgh.15775. Epub 2022 Feb 14.
Ref 296	METTL3 regulates inflammatory pain by modulating m(6)A-dependent pri-miR-365-3p processing. FASEB J. 2020 Jan;34(1):122-132. doi: 10.1096/fj.201901555R. Epub 2019 Nov 19.
Ref 297	Methyltransferase-like 3-mediated N6-methyladenosine modification of miR-7212-5p drives osteoblast differentiation and fracture healing. J Cell Mol Med. 2020 Jun;24(11):6385-6396. doi: 10.1111/jcmm.15284. Epub 2020 Apr 19.
Ref 298	Circ0008399 Interaction with WTAP Promotes Assembly and Activity of the m(6)A Methyltransferase Complex and Promotes Cisplatin Resistance in Bladder Cancer. Cancer Res. 2021 Dec 15;81(24):6142-6156. doi: 10.1158/0008-5472.CAN-21-1518. Epub 2021 Oct 26.
Ref 299	Circ_0008542 in osteoblast exosomes promotes osteoclast-induced bone resorption through m6A methylation. Cell Death Dis. 2021 Jun 18;12(7):628. doi: 10.1038/s41419-021-03915-1.
Ref 300	IFN regulatory Factor-1 induced macrophage pyroptosis by modulating m6A modification of circ_0029589 in patients with acute coronary syndrome. Int Immunopharmacol. 2020 Sep;86:106800. doi: 10.1016/j.intimp.2020.106800. Epub 2020 Jul 13.
Ref 301	Methyltransferase-Like 3-Mediated m6A Methylation of Hsa_circ_0058493 Accelerates Hepatocellular Carcinoma Progression by Binding to YTH Domain-Containing Protein 1. Front Cell Dev Biol. 2021 Nov 23;9:762588. doi: 10.3389/fcell.2021.762588. eCollection 2021.
Ref 302	N6-methyladenosine modification of circCUX1 confers radioresistance of hypopharyngeal squamous cell carcinoma through caspase1 pathway. Cell Death Dis. 2021 Mar 19;12(4):298. doi: 10.1038/s41419-021-03558-2.
Ref 303	A novel protein encoded by circASK1 ameliorates gefitinib resistance in lung adenocarcinoma by competitively activating ASK1-dependent apoptosis. Cancer Lett. 2021 Nov 1;520:321-331. doi: 10.1016/j.canlet.2021.08.007. Epub 2021 Aug 11.
Ref 304	N(6)-methyladenosine-modified circIGF2BP3 inhibits CD8(+) T-cell responses to facilitate tumor immune evasion by promoting the deubiquitination of PD-L1 in non-small cell lung cancer. Mol Cancer. 2021 Aug 20;20(1):105. doi: 10.1186/s12943-021-01398-4.
Ref 305	N(6)-methyladenosine-dependent pri-miR-17-92 maturation suppresses PTEN/TMEM127 and promotes sensitivity to everolimus in gastric cancer. Cell Death Dis. 2020 Oct 9;11(10):836. doi: 10.1038/s41419-020-03049-w.
Ref 306	Long noncoding RNA pncRNA-D reduces cyclin D1 gene expression and arrests cell cycle through RNA m(6)A modification. J Biol Chem. 2020 Apr 24;295(17):5626-5639. doi: 10.1074/jbc.RA119.011556. Epub 2020 Mar 12.
Ref 307	Loss of m(6)A methyltransferase METTL3 promotes heart regeneration and repair after myocardial injury. Pharmacol Res. 2021 Dec;174:105845. doi: 10.1016/j.phrs.2021.105845. Epub 2021 Aug 21.
Ref 308	METTL3 mediates Ang-II-induced cardiac hypertrophy through accelerating pri-miR-221/222 maturation in an m6A-dependent manner. Cell Mol Biol Lett. 2022 Jul 14;27(1):55. doi: 10.1186/s11658-022-00349-1.
Ref 309	Overexpression of m6A-factors METTL3, ALKBH5, and YTHDC1 alters HPV16 mRNA splicing. Virus Genes. 2022 Apr;58(2):98-112. doi: 10.1007/s11262-022-01889-6. Epub 2022 Feb 21.
Ref 310	N(6)-methyladenosine mediates the cellular proliferation and apoptosis via microRNAs in arsenite-transformed cells. Toxicol Lett. 2018 Aug;292:1-11. doi: 10.1016/j.toxlet.2018.04.018. Epub 2018 Apr 20.
Ref 311	N(6) -Methyladenosine Negatively Regulates Human Respiratory Syncytial Virus Replication. Front Cell Dev Biol. 2021 Oct 4;9:739445. doi: 10.3389/fcell.2021.739445. eCollection 2021.
Ref 312	Interplay of m(6) A and histone modifications contributes to temozolomide resistance in glioblastoma. Clin Transl Med. 2021 Sep;11(9):e553. doi: 10.1002/ctm2.553.
Ref 313	N?-Methyladenosine Landscape of Glioma Stem-Like Cells: METTL3 Is Essential for the Expression of Actively Transcribed Genes and Sustenance of the Oncogenic Signaling. Genes (Basel). 2019 Feb 13;10(2):141. doi: 10.3390/genes10020141.
Ref 314	Association between METTL3 gene polymorphisms and neuroblastoma susceptibility: A nine-centre case-control study. J Cell Mol Med. 2020 Aug;24(16):9280-9286. doi: 10.1111/jcmm.15576. Epub 2020 Jul 2.
Ref 315	Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia. Nature. 2021 May;593(7860):597-601. doi: 10.1038/s41586-021-03536-w. Epub 2021 Apr 26.
Ref 316	Overexpression of methyltransferase-like 3 and 14 in oral squamous cell carcinoma. J Oral Pathol Med. 2022 Feb;51(2):134-145. doi: 10.1111/jop.13256. Epub 2021 Nov 3.
Ref 317	RNA methylation-mediated LINC01559 suppresses colorectal cancer progression by regulating the miR-106b-5p/PTEN axis. Int J Biol Sci. 2022 Apr 24;18(7):3048-3065. doi: 10.7150/ijbs.70630. eCollection 2022.
Ref 318	Gene Signature and Identification of Clinical Trait-Related m(6) A Regulators in Pancreatic Cancer. Front Genet. 2020 Jul 10;11:522. doi: 10.3389/fgene.2020.00522. eCollection 2020.
Ref 319	The epitranscriptome m6A writer METTL3 promotes chemo- and radioresistance in pancreatic cancer cells. Int J Oncol. 2018 Feb;52(2):621-629. doi: 10.3892/ijo.2017.4219. Epub 2017 Dec 7.
Ref 320	The RNA m6A methyltransferase METTL3 promotes pancreatic cancer cell proliferation and invasion. Pathol Res Pract. 2019 Nov;215(11):152666. doi: 10.1016/j.prp.2019.152666. Epub 2019 Sep 24.
Ref 321	Contributions and Prognostic Values of N6-Methyladenosine RNA Methylation Regulators in Hepatocellular Carcinoma. Front Genet. 2021 Jan 15;11:614566. doi: 10.3389/fgene.2020.614566. eCollection 2020.
Ref 322	The Role of RNA Methyltransferase METTL3 in Hepatocellular Carcinoma: Results and Perspectives. Front Cell Dev Biol. 2021 May 11;9:674919. doi: 10.3389/fcell.2021.674919. eCollection 2021.
Ref 323	The cancer-testis lncRNA lnc-CTHCC promotes hepatocellular carcinogenesis by binding hnRNP K and activating YAP1 transcription. Nat Cancer. 2022 Feb;3(2):203-218. doi: 10.1038/s43018-021-00315-4. Epub 2022 Jan 10.
Ref 324	MiR-33a suppresses proliferation of NSCLC cells via targeting METTL3 mRNA. Biochem Biophys Res Commun. 2017 Jan 22;482(4):582-589. doi: 10.1016/j.bbrc.2016.11.077. Epub 2016 Nov 14.
Ref 325	miR-302a-3p suppresses melanoma cell progression via targeting METTL3. J Chemother. 2022 Feb;34(1):55-66. doi: 10.1080/1120009X.2021.1953886. Epub 2021 Jul 21.
Ref 326	METTL3 regulates m6A in endometrioid epithelial ovarian cancer independently of METTl14 and WTAP. Cell Biol Int. 2020 Dec;44(12):2524-2531. doi: 10.1002/cbin.11459. Epub 2020 Sep 11.
Ref 327	Connecting METTL3 and intratumoural CD33(+) MDSCs in predicting clinical outcome in cervical cancer. J Transl Med. 2020 Oct 15;18(1):393. doi: 10.1186/s12967-020-02553-z.
Ref 328	Gene signatures and prognostic values of m6A regulators in clear cell renal cell carcinoma - a retrospective study using TCGA database. Aging (Albany NY). 2019 Mar 15;11(6):1633-1647. doi: 10.18632/aging.101856.
Ref 329	Interplay between RNA Methylation Eraser FTO and Writer METTL3 in Renal Clear Cell Carcinoma Patient Survival. Recent Pat Anticancer Drug Discov. 2021;16(3):363-376. doi: 10.2174/1574892816666210204125155.
Ref 330	RNA N (6)-Methyladenosine Modification in Normal and Malignant Hematopoiesis. Adv Exp Med Biol. 2019;1143:75-93. doi: 10.1007/978-981-13-7342-8_4.
Ref 331	The RNA Methyltransferase Complex of WTAP, METTL3, and METTL14 Regulates Mitotic Clonal Expansion in Adipogenesis. Mol Cell Biol. 2018 Jul 30;38(16):e00116-18. doi: 10.1128/MCB.00116-18. Print 2018 Aug 15.
Ref 332	Abnormality of m6A mRNA Methylation Is Involved in Alzheimer's Disease. Front Neurosci. 2020 Feb 28;14:98. doi: 10.3389/fnins.2020.00098. eCollection 2020.
Ref 333	METTL3-dependent RNA m(6)A dysregulation contributes to neurodegeneration in Alzheimer's disease through aberrant cell cycle events. Mol Neurodegener. 2021 Sep 30;16(1):70. doi: 10.1186/s13024-021-00484-x.
Ref 334	Altered Expression of the m6A Methyltransferase METTL3 in Alzheimer's Disease. eNeuro. 2020 Sep 8;7(5):ENEURO.0125-20.2020. doi: 10.1523/ENEURO.0125-20.2020. Print 2020 Sep/Oct.
Ref 335	METTL3 regulates skeletal muscle specific miRNAs at both transcriptional and post-transcriptional levels. Biochem Biophys Res Commun. 2021 May 7;552:52-58. doi: 10.1016/j.bbrc.2021.03.035. Epub 2021 Mar 17.
Ref 336	Distinct roles of Fto and Mettl3 in controlling development of the cerebral cortex through transcriptional and translational regulations. Cell Death Dis. 2021 Jul 14;12(7):700. doi: 10.1038/s41419-021-03992-2.
Ref 337	METTL3 attenuates proliferative vitreoretinopathy and epithelial-mesenchymal transition of retinal pigment epithelial cells via wnt/Beta-catenin pathway. J Cell Mol Med. 2021 May;25(9):4220-4234. doi: 10.1111/jcmm.16476. Epub 2021 Mar 23.
Ref 338	The N(6)-Methyladenosine mRNA Methylase METTL3 Controls Cardiac Homeostasis and Hypertrophy. Circulation. 2019 Jan 22;139(4):533-545. doi: 10.1161/CIRCULATIONAHA.118.036146.
Ref 339	Resveratrol Attenuates High-Fat Diet Induced Hepatic Lipid Homeostasis Disorder and Decreases m(6)A RNA Methylation. Front Pharmacol. 2020 Dec 18;11:568006. doi: 10.3389/fphar.2020.568006. eCollection 2020.
Ref 340	METTL3 Attenuates LPS-Induced Inflammatory Response in Macrophages via NF-KappaB Signaling Pathway. Mediators Inflamm. 2019 Oct 24;2019:3120391. doi: 10.1155/2019/3120391. eCollection 2019.
Ref 341	METTL3-m(6) A methylase regulates the osteogenic potential of bone marrow mesenchymal stem cells in osteoporotic rats via the Wnt signalling pathway. Cell Prolif. 2022 May;55(5):e13234. doi: 10.1111/cpr.13234. Epub 2022 Apr 25.
Ref 342	Meclofenamic acid represses spermatogonial proliferation through modulating m(6)A RNA modification. J Anim Sci Biotechnol. 2019 Jul 11;10:63. doi: 10.1186/s40104-019-0361-6. eCollection 2019.
Ref 343	Mettl3-/Mettl14-mediated mRNA N(6)-methyladenosine modulates murine spermatogenesis. Cell Res. 2017 Oct;27(10):1216-1230. doi: 10.1038/cr.2017.117. Epub 2017 Sep 15.
Ref 344	METTL3-mediated m6A modification is required for cerebellar development. PLoS Biol. 2018 Jun 7;16(6):e2004880. doi: 10.1371/journal.pbio.2004880. eCollection 2018 Jun.
Ref 345	Multi-omic analysis of altered transcriptome and epigenetic signatures in the UV-induced DNA damage response. DNA Repair (Amst). 2021 Oct;106:103172. doi: 10.1016/j.dnarep.2021.103172. Epub 2021 Jul 15.
Ref 346	Targeting the m(6)A RNA modification pathway blocks SARS-CoV-2 and HCoV-OC43 replication. Genes Dev. 2021 Jul 1;35(13-14):1005-1019. doi: 10.1101/gad.348320.121. Epub 2021 Jun 24.
Ref 347	Discovery of Potent and Selective Inhibitors for G9a-Like Protein (GLP) Lysine Methyltransferase. J Med Chem. 2017 Mar 9;60(5):1876-1891. doi: 10.1021/acs.jmedchem.6b01645. Epub 2017 Feb 14.

m6A Regulator Information

Cite M6AREG

Correspondence

Prof. Feng ZHU

Prof. Shuiping Liu

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