m6A Regulator Information

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

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