m6A Regulator Information

General Information of the m6A Regulator (ID: REG00024)

Regulator Name	YTH domain-containing family protein 1 (YTHDF1)
Synonyms	DF1; Dermatomyositis associated with cancer putative autoantigen 1; DACA-1; C20orf21 Click to Show/Hide
Gene Name	YTHDF1
Sequence	MSATSVDTQRTKGQDNKVQNGSLHQKDTVHDNDFEPYLTGQSNQSNSYPSMSDPYLSSYY PPSIGFPYSLNEAPWSTAGDPPIPYLTTYGQLSNGDHHFMHDAVFGQPGGLGNNIYQHRF NFFPENPAFSAWGTSGSQGQQTQSSAYGSSYTYPPSSLGGTVVDGQPGFHSDTLSKAPGM NSLEQGMVGLKIGDVSSSAVKTVGSVVSSVALTGVLSGNGGTNVNMPVSKPTSWAAIASK PAKPQPKMKTKSGPVMGGGLPPPPIKHNMDIGTWDNKGPVPKAPVPQQAPSPQAAPQPQQ VAQPLPAQPPALAQPQYQSPQQPPQTRWVAPRNRNAAFGQSGGAGSDSNSPGNVQPNSAP SVESHPVLEKLKAAHSYNPKEFEWNLKSGRVFIIKSYSEDDIHRSIKYSIWCSTEHGNKR LDSAFRCMSSKGPVYLLFSVNGSGHFCGVAEMKSPVDYGTSAGVWSQDKWKGKFDVQWIF VKDVPNNQLRHIRLENNDNKPVTNSRDTQEVPLEKAKQVLKIISSYKHTTSIFDDFAHYE KRQEEEEVVRKERQSRNKQ Click to Show/Hide
Family	YTHDF family; YTHDF1 subfamily
Function	Specifically recognizes and binds N6-methyladenosine (m6A)-containing mRNAs, and regulates their stability. M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing. Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT complex. The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) shares m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation. Required to facilitate learning and memory formation in the hippocampus by binding to m6A-containing neuronal mRNAs (By similarity). Acts as a regulator of axon guidance by binding to m6A-containing ROBO3 transcripts (By similarity). Acts as a negative regulator of antigen cross-presentation in myeloid dendritic cells (By similarity). In the context of tumorigenesis, negative regulation of antigen cross-presentation limits the anti-tumor response by reducing efficiency of tumor-antigen cross-presentation (By similarity). Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation. The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules. Click to Show/Hide
Gene ID	54915
Uniprot ID	YTHD1_HUMAN
Regulator Type	WRITER ERASER READER
Mechanism Diagram	Click to View the Original Diagram

Target Genes	Click to View Potential Target Genes of This Regulator

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

YTHDF1 can regulate the m6A methylation of following target genes, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulted from the regulation of certain target gene.

Browse Target Gene related Disease

Browse Target Gene related Drug

Ephrin type-B receptor 2 (ERK/EPHB2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shControl AGS		GSE159425
Regulation		logFC: -7.59E-01 p-value: 2.20E-04
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.91E+00	GSE63591

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

Epidermal growth factor receptor (EGFR)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shControl AGS		GSE159425
Regulation		logFC: -6.10E-01 p-value: 2.21E-04
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.78E+00	GSE63591

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	Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
	Cell migration
	Cell nvasion
In-vitro Model	HuCC-T1	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_0324
	RBE	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_4896
In-vivo Model	For the subcutaneous implantation ICC mouse model, 6-week-old male NCG mice (Jiangsu, China) were randomly enrolled into shNC group and shYTHDF1 group (n = 9); 1 × 10⁶ HuCCT1 cells in 0.1-mL PBS transfected with shNC or shYTHDF1 were subcutaneously inoculated in the right flanks of the mice. For AKT/YapS127A-induced orthotopic ICC mouse model, 16 mice were divided into two groups randomly. For the control group, 20-ug AKT, 30-ug Yap, and 2-ug pCMV/SB plasmids plus 20-ug vector plasmids as control were diluted in 2-mL saline and then were injected into the lateral tail vein within 7 s. For the YTHDF1-overexpressed group, mice were injected with additional 20-ug YTHDF1 plasmids under the same conditions. Mice were sacrificed at 4 weeks after injection, and liver tissues were harvested for analysis.
Response Summary	YTHDF1 regulates the translation of Epidermal growth factor receptor (EGFR) mRNA via binding m6 A sites in the 3'-UTR of EGFR transcript. YTHDF1 is upregulated in ICC and associated with shorter survival of ICC patients.

Forkhead box protein O3 (FOXO3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shNC AGS		GSE166972
Regulation		logFC: 1.07E+00 p-value: 3.17E-02
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.44E+00	GSE63591

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			[4]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib	Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising Forkhead box protein 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 ATG16L1.

Injury of heart [ICD-11: NB31]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[48]
Responsed Disease	Myocardial injury [ICD-11: NB31.Z]
Target Regulation	Up regulation
In-vitro Model	H9c2(2-1)	Normal	Rattus norvegicus	CVCL_0286
In-vivo Model	For exercise-trained rats, SD rats were treadmill trained 5 days per week continuing six weeks. In brief, exercise was carried out on a motor-driven treadmill, set at a 10.5% incline, 5 days per week for 6 weeks in an adjoining room maintained at 20 °C. Running duration and speed were gradually increased more than 22 days to 60 min at 30 m/min, corresponding to about 80% VO2 max, and maintained for 2-3 weeks.

Hexokinase-2 (HK2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shControl AGS		GSE159425
Regulation		logFC: -6.80E-01 p-value: 6.28E-04
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.46E+00	GSE63591

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				[5]
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.

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				[51]
Responsed Disease	Esophageal Squamous Cell Carcinoma [ICD-11: 2B70.1]
Target Regulation	Up regulation
In-vitro Model	HET-1A	Normal	Homo sapiens	CVCL_3702
	Eca-109	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
	TE-10	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1760
In-vivo Model	Six-week-old male nude BALB/C mice were randomly divided into two groups, NC and sh-HCP5#1 groups. 2 × 10⁶ EC109 cells were subcutaneously injected into nude mice and grown for 5 weeks.

Integrin alpha-6 (ITGA6)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shControl AGS		GSE159425
Regulation		logFC: -9.21E-01 p-value: 3.27E-05
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.14E+00	GSE63591

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

Kelch-like ECH-associated protein 1 (KEAP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shControl AGS		GSE159425
Regulation		logFC: 1.01E+00 p-value: 4.73E-09
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.61E+00	GSE63591

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				[7]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
Pathway Response	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 10⁶ p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Kelch-like ECH-associated protein 1 (KEAP1)-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.

Myc proto-oncogene protein (MYC)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	Embryonic stem cells	Mus musculus
Treatment: YTHDF1-/- mESCs Control: Wild type ESCs		GSE147849
Regulation		logFC: -1.55E+00 p-value: 2.76E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.21E+00	GSE63591

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				[8]
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.

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		[9]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Pathway Response	p53 signaling pathway	hsa04115
	Central carbon metabolism in cancer	hsa05230
	PD-L1 expression and PD-1 checkpoint pathway in cancer	hsa05235
Response Summary	This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher programmed death-ligand 1 (PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The Myc proto-oncogene protein (MYC) targets, E2 transcription Factor (E2F) targets were significantly enriched.

PR domain zinc finger protein 2 (PRDM2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shNC AGS		GSE166972
Regulation		logFC: 2.20E+00 p-value: 3.42E-04
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.84E+00	GSE63591

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				[10]
Responsed Disease	Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Responsed Drug	Arsenite		Phase 2	Drug Info
Target Regulation	Down regulation
Pathway Response	p53 signaling pathway			hsa04115
In-vitro Model	HaCaT	Normal	Homo sapiens	CVCL_0038
Response Summary	METTL3 significantly decreased m6A level, restoring p53 activation and inhibiting cellular transformation phenotypes in the arsenite-transformed cells. m6A downregulated the expression of the positive p53 regulator, PR domain zinc finger protein 2 (PRDM2), through the YTHDF2-promoted decay of PRDM2 mRNAs. m6A upregulated the expression of the negative p53 regulator, YY1 and MDM2 through YTHDF1-stimulated translation of YY1 and MDM2 mRNA. This study further sheds light on the mechanisms of arsenic carcinogenesis via RNA epigenetics.

TNF receptor-associated factor 4 (TRAF4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shControl AGS		GSE159425
Regulation		logFC: 8.33E-01 p-value: 9.45E-04
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.38E+00	GSE63591

Obesity [ICD-11: 5B81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[11]
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120), Proteasome
Cell Process	Ubiquitination degradation
In-vitro Model	SVF (Stromal vascular cell fraction (SVF) was isolated from minced inguinal adipose tissue of male C57BL/6J mice (3-4 weeks old))
	3T3-L1	Normal	Mus musculus	CVCL_0123
In-vivo Model	Before the tests, animals were fasted for 8 h. l glucose tolerance test (GTT) was conducted during week 11 on the diet. The mice were challenged with 2 g/kg body weight d-glucose (Sigma-Aldrich, USA). Insulin tolerance test (ITT) was conducted during week 12 on the diet. For insulin tolerance test, mice were injected intraperitoneally with 0.75 U/kg body weight insulin (Sigma-Aldrich, USA). For both tests, blood samples were taken from the tail vein and glucose levels were measured at indicated time points after administration using an AlphaTRAK glucometer.
Response Summary	m6A-dependent TNF receptor-associated factor 4 (TRAF4) expression upregulation by ALKBH5 and YTHDF1 contributes to curcumin-induced obesity prevention.

Transcription factor E2F8 (E2F8)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shControl AGS		GSE159425
Regulation		logFC: -8.62E-01 p-value: 7.08E-04
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.18E+00	GSE63591

Breast cancer [ICD-11: 2C60]

In total 3 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]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stability
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	Hs 578T	Invasive breast carcinoma	Homo sapiens	CVCL_0332
In-vivo Model	1×10⁶ MDA-MB-231 cells were resuspended in 100 uL PBS with 50% Matrigel (Corning Costar, USA), and injected into the mammary fat pad of the mice.
Response Summary	In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stability
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	Hs 578T	Invasive breast carcinoma	Homo sapiens	CVCL_0332
In-vivo Model	1×10⁶ MDA-MB-231 cells were resuspended in 100 uL PBS with 50% Matrigel (Corning Costar, USA), and injected into the mammary fat pad of the mice.
Response Summary	In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner.
Experiment 3 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Olaparib		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stability
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	Hs 578T	Invasive breast carcinoma	Homo sapiens	CVCL_0332
In-vivo Model	1×10⁶ MDA-MB-231 cells were resuspended in 100 uL PBS with 50% Matrigel (Corning Costar, USA), and injected into the mammary fat pad of the mice.
Response Summary	In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner.

Transcriptional coactivator YAP1 (YAP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shNC AGS		GSE166972
Regulation		logFC: 3.89E+00 p-value: 1.09E-02
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.35E+00	GSE63591

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				[13]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Up regulation
Cell Process	Cell growth
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
In-vivo Model	Three-week-old BABL/c female nude mice were randomized into three groups. 5 × 10⁶ 143B cells were subcutaneously injected in mice, and the tumor volume was assessed every 2 weeks. Eight weeks after injection, the animals were killed. The xenograft tumors were harvested and the tumor volumes were calculated by the standard formula: length × width²/2.
Response Summary	ALKBH5 is an anti-tumor factor or a pro-apoptotic factor, acting at least partially by suppressing Transcriptional coactivator YAP1 (YAP1) expression through dual mechanisms with direct m6A methylation of YAP and indirect downregulation of YAP level due to methylation of pre-miR-181b-1. Further results revealed that m6A methylated pre-miR-181b-1 was subsequently recognized by m6A-binding protein YTHDF2 to mediate RNA degradation. However, methylated YAP transcripts were recognized by YTHDF1 to promote its translation. ALKBH5 overexpression was considered a new approach of replacement therapy for osteosarcoma treatment.

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				[14]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 10⁶ lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-Transcriptional coactivator YAP1 (YAP1) axis to induce Non-small cell lung cancer drug resistance and metastasis.

Kidney disorders [ICD-11: GB90]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[15]
Responsed Disease	Kidney disorders [ICD-11: GB90]
Target Regulation	Up regulation
Response Summary	YTHDF1 knockdown alleviated the progression of renal fibrosis both in cultured cells induced by transforming growth factor-beta administration and in the UUO mouse model. Transcriptional coactivator YAP1 (YAP1) was accordingly down-regulated when YTHDF1 was inhibited.

Adenosine 5'-monophosphoramidase HINT2 (HINT2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shControl AGS		GSE159425
Regulation		logFC: 8.82E-01 p-value: 1.64E-04
More Results	Click to View More RNA-seq Results

Melanoma [ICD-11: 2C30]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[16]
Responsed Disease	Melanoma [ICD-11: 2C30]
Target Regulation	Up regulation
In-vitro Model	CM2005.1	Conjunctival melanoma	Homo sapiens	CVCL_M592
	CRMM-1	Conjunctival melanoma	Homo sapiens	CVCL_M593
	HEK293T	Normal	Homo sapiens	CVCL_0063
	OCM-1	Amelanotic melanoma	Homo sapiens	CVCL_6934
	OCM-1A	Amelanotic melanoma	Homo sapiens	CVCL_6935
	OM431	Uveal melanoma	Homo sapiens	CVCL_J308
	PIG1	Normal	Homo sapiens	CVCL_S410
In-vivo Model	Approximately 1 × 10⁶ melanoma cells from each group were injected subcutaneously into the right side of the abdomen of BALB/c nude mice (male, 6 weeks old).
Response Summary	YTHDF1 promoted the translation of methylated Adenosine 5'-monophosphoramidase HINT2 (HINT2) mRNA, a tumor suppressor in ocular melanoma.

Autophagy-related protein 16-1 (ATG16L1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shNC AGS		GSE166972
Regulation		logFC: -1.37E+00 p-value: 3.41E-02
More Results	Click to View More RNA-seq Results

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[4]
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).

Beclin-1 (BECN1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shNC AGS		GSE166972
Regulation		logFC: -1.33E+00 p-value: 2.29E-02
More Results	Click to View More RNA-seq Results

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[17]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib	Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Ferroptosis		hsa04216
	Autophagy		hsa04140
Cell Process	Ferroptosis
	Cell autophagy
In-vitro Model	HSC (Hematopoietic stem cell)
In-vivo Model	VA-Lip-Mettl4-shRNA, VA-Lip-Fto-Plasmid and VA-Lip-Ythdf1-shRNA (0.75 mg/kg) were injected intravenously 3 times a week.
Response Summary	Analyzed the effect of sorafenib on HSC ferroptosis and m6A modification in advanced fibrotic patients with hepatocellular carcinoma receiving sorafenib monotherapy. YTHDF1 promotes Beclin-1 (BECN1) mRNA stability and autophagy activation via recognizing the m6A binding site within BECN1 coding regions.

Cyclin-dependent kinase 2 (CDK2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shControl AGS		GSE159425
Regulation		logFC: -8.20E-01 p-value: 7.96E-07
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[7]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
Pathway Response	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 10⁶ p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of Cyclin-dependent kinase 2 (CDK2), CDK4, p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.

Forkhead box protein M1 (FOXM1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shNC AGS		GSE166972
Regulation		logFC: -8.94E-01 p-value: 2.29E-02
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transformation
	Cell proliferation
	Cell invasion
In-vitro Model	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	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
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
In-vivo Model	NOD/SCID immune-deficient mice were purchased from Shanghai Experimental Animal Center. 2 * 10⁶ MCF-7 cells transduced with sh-NC or sh-YTHDF1-were subcutaneously injected into the mice (5/group). Tumor width and length were measured every 7 days. Tumor volume = (length * width2)/2. After 7 weeks, mice were sacrificed, and the weight of tumors was detected. Xenografts were collected for HE staining, immunohistochemistry staining and western blot analysis.For spontaneous lung metastasis assay, 4 * 10⁶ sh-NC or sh-YTHDF1#2 transduced MCF-7 cells were injected into the mammary fat pads of the NOD/SCID mice (5/group). The primary tumor was removed when its volume reached 150 mm3. The mice were sacrificed, and lung metastasis nodules were counted 12 weeks after the removal.
Response Summary	Forkhead box protein M1 (FOXM1) is a target of YTHDF1. Through recognizing and binding to the m6A-modified mRNA of FOXM1, YTHDF1 accelerated the translation process of FOXM1 and promoted breast cancer metastasis.

Multiple myeloma [ICD-11: 2A83]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[46]
Responsed Disease	Multiple myeloma [ICD-11: 2A83.1]
In-vitro Model	NCI-H929	Plasma cell myeloma	Homo sapiens	CVCL_1600
	MM1.S	Plasma cell myeloma	Homo sapiens	CVCL_8792
	U266B1	Plasma cell myeloma	Homo sapiens	CVCL_0566
	CAG	Plasma cell myeloma	Homo sapiens	CVCL_D569

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		[47]
Responsed Disease	Pulmonary arterial hypertension [ICD-11: BB01.0]
Target Regulation	Up regulation
In-vivo Model	Twenty-four C57BL/6 mice, 6-8-week-old, weighing 20-25 g, were obtained from the animal center of Nanchang University. All the animals were raised in specific-pathogen-free (SPF) conditions in a 12-h light-dark cycle and supplied with free food and water. The animal experiments were conducted following the standard guidelines and permitted by the ethics committee of The First Affiliated Hospital of Nanchang University. The mice were randomly assigned into 4 groups (n = 6 per group). Mice in the control (normoxia) group were housed at 21% O2 (room air) for 4 weeks. Mice in the PAH (hypoxia) group were housed in a chamber with 10% O2 and 90% N2 for 4 weeks. The chamber has an adsorption-type oxygen concentrator to control the flow rates of compressed air and nitrogen (Teijin, Tokyo, Japan). Mice in the PAH + si-YTHDF1 group received a tail vein injection of adenovirus containing si-YTHDF1 (Ad-si-YTHDF1). Mice in the PAH + si-NC group received a tail vein injection of Ad-si-NC. The adenovirus was immediately injected when hypoxia subjection and the adenovirus dose was 1.0 × 109 PFU with 100 μL saline for each mouse.

Insulin-like growth factor I (IGF1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shNC AGS		GSE166972
Regulation		logFC: -1.17E+00 p-value: 4.12E-02
More Results	Click to View More RNA-seq Results

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		[19]
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.

Nucleolar protein 3 (ARC)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shControl AGS		GSE159425
Regulation		logFC: 8.08E-01 p-value: 1.08E-05
More Results	Click to View More RNA-seq Results

Alzheimer disease [ICD-11: 8A20]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[20]
Responsed Disease	Alzheimer disease [ICD-11: 8A20]
Target Regulation	Up regulation
In-vitro Model	SH-SY5Y	Neuroblastoma	Homo sapiens	CVCL_0019
Response Summary	METTL3 rescues the A-Bete-induced reduction of Nucleolar protein 3 (ARC) expression via YTHDF1-Dependent m6A modification, which suggests an important mechanism of epigenetic alteration in AD.

Pyruvate kinase PKM (PKM2/PKM)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shControl AGS		GSE159425
Regulation		logFC: 6.97E-01 p-value: 4.17E-05
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[21]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
Pathway Response	HIF-1 signaling pathway			hsa04066
Cell Process	Glycolysis
In-vitro Model	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	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
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
In-vivo Model	Each mouse was injected subcutaneously with 5 × 10⁶ units of tumor cells to construct the tumor model.
Response Summary	Tumor hypoxia can transcriptionally induce HIF1alpha and post-transcriptionally inhibit the expression of miR-16-5p to promote YTHDF1 expression, which could sequentially enhance tumor glycolysis by upregulating Pyruvate kinase PKM (PKM2/PKM) and eventually increase the tumorigenesis and metastasis potential of breast cancer cells.

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

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shNC AGS		GSE166972
Regulation		logFC: -2.24E+00 p-value: 7.14E-03
More Results	Click to View More RNA-seq Results

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[22]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	Epithelial-mesenchymal transition
	Cell migration
	Cell invasion
	Cell proliferation
In-vitro Model	SNU-398	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0077
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
In-vivo Model	Ten four-week-old BALB/c male nude mice (GemPharmatech, Jiangsu, China) were subcutaneously injected with control Huh7 cells 2 × 10⁶ (left-back) and stable knockdown of YTHDF1 Huh7 cells 2 × 10⁶ (right-back). These cells were respectively premixed with 50 ul Matrigel (Corning, 354,234) in 100 ul PBS.
Response Summary	YTHDF1 contributes to the progression of HCC by activating PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR signaling pathway and inducing EMT.

Transcription factor E2F1 (E2F1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shNC AGS		GSE166972
Regulation		logFC: -6.62E-01 p-value: 3.39E-02
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[9]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Pathway Response	p53 signaling pathway	hsa04115
	Central carbon metabolism in cancer	hsa05230
	PD-L1 expression and PD-1 checkpoint pathway in cancer	hsa05235
Response Summary	This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher programmed death-ligand 1 (PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, Transcription factor E2F1 (E2F1) targets were significantly enriched.

Tripartite motif-containing protein 29 (TRIM29)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shNC AGS		GSE166972
Regulation		logFC: 2.23E+00 p-value: 1.11E-02
More Results	Click to View More RNA-seq Results

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[23]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Cell Process	Ectopic expression
In-vitro Model	A2780	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
In-vitro Model	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vivo Model	The specified number of viable SKOV3/DDP cells and SKOV3/DDP cells with TRIM29 knock down were resuspended in 100 uL PBS, injected subcutaneously under the left and right back of 4-week old nude mice respectively (n = 3 per group).
Response Summary	m6A-YTHDF1-mediated Tripartite motif-containing protein 29 (TRIM29) upregulation facilitates the stem cell-like phenotype of cisplatin-resistant ovarian cancer cells. TRIM29 acts as an oncogene to promote the CSC-like features of cisplatin-resistant ovarian cancer in an m6A-YTHDF1-dependent manner.

Ubiquitin carboxyl-terminal hydrolase 14 (USP14)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shNC AGS		GSE166972
Regulation		logFC: -1.83E+00 p-value: 4.80E-05
More Results	Click to View More RNA-seq Results

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[24]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Cell Process	Cell proliferation and invasion
Cell Process	Cell apoptosis
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	GES-1	Normal	Homo sapiens	CVCL_EQ22
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
	MKN28	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_1416
	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
In-vivo Model	BGC-823 cells (5 × 10⁶) with shRNAs targeting YTHDF1 (sh-YTHDF1) or shRNAs targeting control (sh-NC) were trypsinized and suspended in 0.1 mL PBS and injected subcutaneously into the BALB/c mice (n = 5 mice per group).
Response Summary	YTHDF1 promoted Ubiquitin carboxyl-terminal hydrolase 14 (USP14) protein translation in an m6A-dependent manner. USP14 upregulation was positively correlated with YTHDF1 expression and indicated a poor prognosis in gastric cancer.

Apoptosis regulator Bcl-2 (BCL2)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.25E+00	GSE63591

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				[25]
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.

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				[25]
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.

Autophagy-related protein 2 homolog A (ATG2A)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.31E+00	GSE63591

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				[26]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
	HIF-1 signaling pathway			hsa04066
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell autophagy
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	HCC cells (1 × 10⁶/100 uL PBS) were administered to 4-week-old female BALB/c nude mice by subcutaneous injection (n = 6).
Response Summary	HIF-1-alpha-induced YTHDF1 expression was associated with hypoxia-induced autophagy and autophagy-related hepatocellular carcinoma progression via promoting translation of autophagy-related genes Autophagy-related protein 2 homolog A (ATG2A) and ATG14 in a m6A-dependent manner.

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

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.78E+00	GSE63591

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

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[27]
Responsed Disease	Non-alcoholic fatty liver disease [ICD-11: DB92]
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cell autophagy
In-vitro Model	AML12	Normal	Mus musculus	CVCL_0140
	Hepa 1-6	Hepatocellular carcinoma of the mouse	Mus musculus	CVCL_0327
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
In-vivo Model	All mice were housed in specific pathogen-free conditions in the animal facility with constant temperature and humidity under a 12-h light/12-h dark cycle, with free access to water and food. After a week of adaptation, they were then divided into two groups randomly and fed with a HFD (60 kcal% fat, D12492, Research Diets) or standard normal chow diet (CD) for 16 weeks, respectively.
Response Summary	The upregulation of METTL3 and YTHDF1 induced by lipotoxicity contributes to the elevated expression level of Beclin-1 associated RUN domain containing protein (RUBCN/Rubicon) in an m6A-dependent manner, which inhibits the fusion of autophagosomes and lysosomes and further suppresses the clearance of LDs via lysosomes in nonalcoholic fatty liver disease.

Catenin beta-1 (CTNNB1/Beta-catenin)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.05E+00	GSE63591

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				[28]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Pathway Response	Signaling pathways regulating pluripotency of stem cells			hsa04550
Cell Process	Cell Tumorigenicity
In-vitro Model	NCM460	Normal	Homo sapiens	CVCL_0460
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	1 × 10⁵ parental HT29-shNC cells, HT29-shYTHDF1 cells, HT29-shNC colonospheres, and HT29-shYTHDF1 colonospheres were inoculated subcutaneously into the left inguinal folds of the nude mice.
Response Summary	Silencing YTHDF1 significantly inhibited Wnt/Catenin beta-1 (CTNNB1/Beta-catenin) pathway activity in Colorectal cancer cells.

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				[29]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell invasion
	Cell migration
	Cell apoptosis
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-1650 (Non-Small Cell Lung Cancer Cells)
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H358	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1559
Response Summary	ECs transmitted miR-376c into NSCLC cells through Evs, and inhibited the intracellular YTHDF1 expression and the Wnt/Catenin beta-1 (CTNNB1/Beta-catenin) pathway activation. YTHDF1 overexpression reversed the inhibitory role of miR-376c released by EC-Evs in non-small cell lung cancer cells.

E3 SUMO-protein ligase RanBP2 (RANBP2)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.70E+00	GSE63591

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				[30]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulation	Up regulation
Cell Process	Cell growth
	Cell migration
	Cell invasion
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
In-vivo Model	Balb/c female nude mice at 4-6 weeks old were injected with 4 × 10⁶ cells subcutaneously on the back.
Response Summary	The oncogenic role of YTHDF1 in cervical cancer by regulating E3 SUMO-protein ligase RanBP2 (RANBP2) expression and YTHDF1 represents a potential target for cervical cancer therapy.

Frizzled-7 (FZD7)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.73E+00	GSE63591

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				[31]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
In-vitro Model	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
In-vitro Model	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
In-vivo Model	Stable short hairpin (shRNA)-expressing MGC-803 cells (3 × 10⁶) were suspended in 0.1 mL PBS and injected into the flanks of BALB/c mice (n = 8 mice/group) at 5-6 weeks of age. For the flanks injected mice, tumor growth was examined every 3 days. After 5 weeks, mice were sacrificed by cervical dislocation, and weight of xenografts was tested.BALB/c mice were randomly divided into three groups (n = 4 mice/group). A total of 3 × 10⁶ stable shRNA-expressing MGC-803 cells were resuspended in 0.1 mL PBS and injected into the abdominal cavity. After 4 weeks, mice were sacrificed by cervical dislocation, abdominal cavities were opened, and the numbers of implantation metastasis were counted.For the pulmonary metastasis model, NOD/SCID mice were randomly divided into three groups (n = 4 mice/group). A total of 1 × 10⁵ stable shRNA-expressing MGC-803 cells were resuspended in 0.1 mL PBS and injected into the lateral tail vein. After 7 weeks, mice were sacrificed by cervical dislocation, and lungs were extracted and fixed 4% paraformaldehyde in PBS. Paraffin embedding, sectioning, and staining with hematoxylin and eosin were performed. Visible lung metastases were measured and counted using a microscope.
Response Summary	Mutated YTHDF1 enhanced expression of Frizzled-7 (FZD7), leading to hyperactivation of the Wnt/Bete-catenin pathway and promotion of gastric cancer carcinogenesis.

Poly [ADP-ribose] polymerase 1 (PARP1)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.06E+00	GSE63591

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				[32]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Responsed Drug	Oxaliplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
	Signaling pathways regulating pluripotency of stem cells			hsa04550
Cell Process	RNA stability
	Excision repair
In-vitro Model	SNU-719	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_5086
	MKN74	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_2791
	HEK293T	Normal	Homo sapiens	CVCL_0063
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
In-vivo Model	100,000 pLKO and PARP1-sh1 (PT1 and PT2) cells were mixed with matrix gel and inoculate into BALB/C nude mice, respectively. After 25 days, 6 organoid transplanted tumor mice were treated with oxaliplatin (Sellekchem, s1224) twice a week for 4 weeks at a dose of 5 mg/kg.
Response Summary	m6A methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting PARP1 mRNA stability which increases base excision repair pathway activity. METTTL3 enhances the stability of PARP1 by recruiting Poly [ADP-ribose] polymerase 1 (PARP1) to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA.

Protein phosphatase 1A (PPM1A)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.22E+00	GSE63591

Male infertility [ICD-11: GB04]

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	Azoospermia [ICD-11: GB04.0]
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	RNA stability
	Cell autophagy
In-vitro Model	TM3	Normal	Mus musculus	CVCL_4326
In-vivo Model	Male SPF BALB/c mice (qls02-0202) were purchased from Qinglongshan animal breeding farm. Mice were sacrificed by CO₂ asphyxiation and testes were obtained for following histopathological analyses.
Response Summary	m6A modification promoted translation of Protein phosphatase 1A (PPM1A) (protein phosphatase 1A, magnesium dependent, alpha isoform), a negative AMP-activated protein kinase (AMPK) regulator, but decreased expression of CAMKK2 (calcium/calmodulin-dependent protein kinase kinase 2, beta), a positive AMPK regulator, by reducing its RNA stability. Similar regulation of METTL14, ALKBH5, and m6A was also observed in LCs upon treatment with human chorionic gonadotropin (HsCG). Knock down of YTHDF1 failed to change the expression of CAMKK2 Providing insight into novel therapeutic strategies by exploiting m6A RNA methylation as targets for treating azoospermatism and oligospermatism patients with reduction in serum testosterone. Rapamycin could effectively inhibit phosphorylation of RPS6KB1.

Rho guanine nucleotide exchange factor 2 (ARHGEF2)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.80E+00	GSE63591

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				[34]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
In-vitro Model	SW1116	Colon adenocarcinoma	Homo sapiens	CVCL_0544
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	LS180	Colon adenocarcinoma	Homo sapiens	CVCL_0397
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
Response Summary	YTHDF1 promotes cell growth in CRC cell lines and primary organoids and lung and liver metastasis in vivo. YTHDF1 binds to m6A sites of Rho guanine nucleotide exchange factor 2 (ARHGEF2) messenger RNA, resulting in enhanced translation of ARHGEF2.

Serine/threonine-protein kinase mTOR (MTOR)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.73E+00	GSE63591

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				[22]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151), mTOR signaling pathway
Cell Process	Epithelial-mesenchymal transition
	Cell migration
	Cell invasion
	Cell proliferation
In-vitro Model	SNU-398	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0077
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
In-vivo Model	Ten four-week-old BALB/c male nude mice (GemPharmatech, Jiangsu, China) were subcutaneously injected with control Huh7 cells 2 × 10⁶ (left-back) and stable knockdown of YTHDF1 Huh7 cells 2 × 10⁶ (right-back). These cells were respectively premixed with 50 ul Matrigel (Corning, 354,234) in 100 ul PBS.
Response Summary	YTHDF1 contributes to the progression of HCC by activating PI3K/AKT/Serine/threonine-protein kinase mTOR (MTOR) signaling pathway and inducing EMT.

Signal transducer and activator of transcription 2 (STAT2)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.30E+00	GSE63591

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				[35]
Responsed Disease	Congenital pneumonia [ICD-11: KB24]
Target Regulation	Down regulation
Cell Process	Cell apoptosis
In-vitro Model	WI-38	Normal	Homo sapiens	CVCL_0579
In-vivo Model	All mice were housed under a 12 h light/dark cycle with constant temperature about 25 ℃ and relative humidity approximating 55 %. The mice had free access to food and water for 10 days prior to the experiment. Forty mice were randomly selected and divided into four groups of 10 mice each. After 10 days, mice received an intraperitoneal injection of 22 mg / mL sodium pentobarbital (diluted in saline) followed by 167 uM LPS (60 uL) Saline solution was instilled into the oral cavity through the posterior pharyngeal wall. Pinch the nares quickly and hold for 30 s, model is successful when all fluid is absorbed into the nasal cavity, and slight tracheal rales appear. Lentiviral vectors containing pcDNA-SNHG4 (150 uM) or pcDNA-3.1 were intratracheally injected into mice. Twenty-one days after establishing the model, mice were intraperitoneally injected with 3% sodium pentobarbital and euthanized by overdose anesthesia at a dose of 90 mL/Kg, and organs and tissues were removed for follow-up studies.
Response Summary	SNHG4 was downregulated in the neonatal pneumonia patient serum and its overexpression could inhibit LPS induced inflammatory injury in human lung fibroblasts and mouse lung tissue. The molecular mechanism underlying this protective effect was achieved by suppression of METTL3-mediated m6A modification levels of YTHDF1-dependent Signal transducer and activator of transcription 2 (STAT2) mRNA.

Transferrin receptor protein 1 (TFRC)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.40E+00	GSE63591

Hypopharyngeal cancer [ICD-11: 2B6D]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[36]
Responsed Disease	Hypopharyngeal squamous cell carcinoma [ICD-11: 2B6D.0]
Target Regulation	Up regulation
Pathway Response	Ferroptosis			hsa04216
Cell Process	Ferroptosis
In-vitro Model	YCU-MS861	Maxillary sinus squamous cell carcinoma	Homo sapiens	CVCL_8021
	YCU-MS861	Maxillary sinus squamous cell carcinoma	Homo sapiens	CVCL_8021
	FaDu	Hypopharyngeal squamous cell carcinoma	Homo sapiens	CVCL_1218
	Detroit 562	Pharyngeal squamous cell carcinoma	Homo sapiens	CVCL_1171
Response Summary	YTHDF1 enhanced Transferrin receptor protein 1 (TFRC) expression in HPSCC through an m6A-dependent mechanism.

Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.44E+00	GSE63591

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				[14]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 10⁶ lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.

Aldo-keto reductase family 1 member C1 (AKR1C1)

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[7]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
Pathway Response	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 10⁶ p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nrf2-Aldo-keto reductase family 1 member C1 (AKR1C1) axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.

Alpha-enolase (ENO1)

Target Gene

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[37]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
In-vitro Model	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
	RT-4	Bladder carcinoma	Homo sapiens	CVCL_0036
	J82	Bladder carcinoma	Homo sapiens	CVCL_0359
	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	For the subcutaneous implantation model, 5 × 10⁶ cells (n = 6 per group) were subcutaneously injected into the flank regions of 4-5 weeks female BALB/c nude mice. Tumor volume was calculated as 0.5 × W2 × L (where W and L represent a tumor's width and length, respectively). After xenografts were generated, DMSOand SB431542 (10 mg/kg, #301836-41-9, SANTA CRUZ BIOTECHNOLOGY), or ENOblock (#1177827-73-4, 10 mg/kg, MCE) were administered daily. All animal experiments were approved by The Affiliated Hospital of Qingdao University Committee on Animal Care.

Autophagy protein 5 (ATG5)

Target Gene

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[4]
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), ATG7, ATG12, and ATG16L1.

Beclin 1-associated autophagy-related key regulator (ATG14)

Target Gene

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[26]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
	HIF-1 signaling pathway			hsa04066
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell autophagy
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	HCC cells (1 × 10⁶/100 uL PBS) were administered to 4-week-old female BALB/c nude mice by subcutaneous injection (n = 6).
Response Summary	HIF-1-alpha-induced YTHDF1 expression was associated with hypoxia-induced autophagy and autophagy-related hepatocellular carcinoma progression via promoting translation of autophagy-related genes ATG2A and Beclin 1-associated autophagy-related key regulator (ATG14) in a m6A-dependent manner.

Caveolin-1 (CAV1)

Target Gene

Vascular Calcification [ICD-11: BE2Y]

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	Vascular Calcification [ICD-11: BE2Y]
In-vitro Model	CHO-S/H9C2	N.A.	Cricetulus griseus	CVCL_A0TS
In-vivo Model	2-month-old mice were given doses of tamoxifen at 40 mg/kg body weight/ day for 5 consecutive days by intraperitoneal injection. Littermate mice with wild-type levels of Ythdf1, either expressing Cre recombinase only or containing the Ythdf1 flox/flox-only, were used as controls (Ctrl). All mice received tamoxifen injections. All in vivo experiments and analyses were performed 1 month after the first tamoxifen injection.

CCR4-NOT transcription complex subunit 7 (CNOT7)

Target Gene

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[39]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	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	The mice were divided into two groups with three mice in each group and their flank was subcutaneously injected with 1 × 10⁷ OS cells. 28 days following subcutaneous injection, the mice were sacrificed through carbon dioxide euthanasia (30%/min) to obtain tumor weight and volume measurements.
Response Summary	YTHDF1 could recognize the m6A sites of CCR4-NOT transcription complex subunit 7 (CNOT7) and promote its expression in an m6A manner. Inhibition of YTHDF1 could suppress the proliferation, migration and invasion of the OS cells.

Cellular tumor antigen p53 (TP53/p53)

Target Gene

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				[10]
Responsed Disease	Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Responsed Drug	Arsenite		Phase 2	Drug Info
Target Regulation	Down 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.

Collagen alpha-1 (III) chain (COL3A1)

Target Gene

Hepatic fibrosis/cirrhosis [ICD-11: DB93]

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	Hepatic fibrosis/cirrhosis [ICD-11: DB93]
Target Regulation	Up regulation
In-vitro Model	JS1	N.A.	Mus musculus	CVCL_C7PL
In-vivo Model	Following 1 week of adaptive feeding, the mice were randomly divided into CCl4 + siCON and CCl4 + siYTHDF1 groups. Both groups were injected intraperitoneally with 5 ml/kg of 10% carbon tetrachloride (CCl4) twice a week for 4 weeks, to establish liver fibrosis.

Cyclin-dependent kinase 4 (CDK4)

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[7]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
Pathway Response	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 10⁶ p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, Cyclin-dependent kinase 4 (CDK4), p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.

Cyclin-dependent kinase inhibitor 1B (CDKN1B/p27)

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[7]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
Pathway Response	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 10⁶ p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, Cyclin-dependent kinase inhibitor 1B (CDKN1B/p27), and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.

DNA (cytosine-5)-methyltransferase 3B (DNMT3B)

Target Gene

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[41]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279

E3 ubiquitin-protein ligase Mdm2 (Mdm2)

Target Gene

Acute kidney failure [ICD-11: GB60]

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	Acute kidney failure [ICD-11: GB60]
Target Regulation	Up regulation
In-vitro Model	HK-2 [Human kidney]	Normal	Homo sapiens	CVCL_0302

Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1/eIF2-Alpha)

Target Gene

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		[43]
Responsed Disease	Pulmonary arterial hypertension [ICD-11: BB01.0]
Target Regulation	Up regulation
In-vivo Model	Adult male Sprague-Dawley (150-200 g in body weight) rats were randomly divided into control or MCT/vehicle rats. Experimental rats were administered an intraperitoneal injection of monocrotaline (60 mg/kg, Sigma, 315-22-0), and their littermates were injected with saline. For GSK2606414 treatment, rats that underwent monocrotaline treatment were treated either with vehicle or GSK2606414 (10 mg/kg, Sigma, 1,337,531-89-1) by intraperitoneal injection per day. GSK2606414 was dissolved in a mixture of dimethyl sulfoxide (DMSO): polyethylene glycol (PEG) 400: distilled water (1: 4: 5). After 4 weeks, RV systolic blood pressure (RVSP) was measured with pressure transducers under anesthesia. The RV hypertrophy was analyzed as a ratio of RV to left ventricular and septal weight. Left lung tissues were fixed in 4% paraformaldehyde solution for the following histology staining; right lung tissues and pulmonary arteries were excised and immediately frozen in liquid nitrogen for other experiments.

Eukaryotic translation initiation factor 3 subunit A (EIF3A/EIF3)

Target Gene

Merkel cell carcinoma [ICD-11: 2C34]

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	Merkel cell carcinoma [ICD-11: 2C34]
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Cell Process	Translation
In-vitro Model	MCC13	Merkel cell carcinoma	Homo sapiens	CVCL_2583
	MCC26	Merkel cell carcinoma	Homo sapiens	CVCL_2585
	MKL-1	Merkel cell carcinoma	Homo sapiens	CVCL_2600
	MKL-2	Merkel cell carcinoma	Homo sapiens	CVCL_D027
	PeTa	Merkel cell carcinoma	Homo sapiens	CVCL_LC73
	UISO-MCC-1	Merkel cell carcinoma	Homo sapiens	CVCL_E996
	WaGa	Merkel cell carcinoma	Homo sapiens	CVCL_E998
Response Summary	Knockdown of YTHDF1 in Merkel cell carcinoma (MCC) cell lines negatively affected the translation initiation factor Eukaryotic translation initiation factor 3 subunit A (EIF3A/EIF3) and reduced proliferation and clonogenic capacity in vitro.

Eukaryotic translation initiation factor 3 subunit C (EIF3C)

Target Gene

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[45]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Cell Process	Tumorigenesis and metastasis
In-vitro Model	A2780	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	HEK293T	Normal	Homo sapiens	CVCL_0063
	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vivo Model	5 × 10⁶ cells in PBS were injected subcutaneously into one side of the posterior flanks of Balb/C nude mice at 6-8 weeks old.
Response Summary	YTHDF1 augments the translation of Eukaryotic translation initiation factor 3 subunit C (EIF3C) in an m6A-dependent manner by binding to m6A-modified EIF3C mRNA and concomitantly promotes the overall translational output, thereby facilitating tumorigenesis and metastasis of ovarian cancer.

G1/S-specific cyclin-D1 (CCND1)

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[7]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
Pathway Response	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 10⁶ p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and G1/S-specific cyclin-D1 (CCND1), and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.

Asthma [ICD-11: CA23]

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	Asthma [ICD-11: CA23]
Target Regulation	Up regulation

Heat shock factor protein 1 (HSF1)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[50]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
In-vitro Model	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
In-vitro Model	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546

Interferon gamma receptor 1 (IFNGR1)

Target Gene

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[52]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation
Pathway Response	JAK-STAT signaling pathway			hsa04630
Cell Process	Immunity
In-vitro Model	YTN16 (Mouse gastric cancer cell line (YTN16))
	MKN74	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_2791
	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
In-vivo Model	MKN74 cells (5×10⁶/tumor) expressing shNC, shYTHDF1-1, or shYTHDF1-2 were suspended in ice-cold 100 ul PBS:Matrigel gel (1:1, v/v) (Corning, USA), and subcutaneously implanted into the right dorsal flank of 4-week-old NOD.
Response Summary	Loss of YTHDF1 mediated the overexpression of Interferon gamma receptor 1 (IFNGR1) and JAK/STAT1 signaling pathway in tumor cells, which contributes to restored sensitivity to antitumor immunity. YTHDF1 is overexpressed in GC and promotes GC by inducing cell proliferation and repression of DCs-mediated antitumor immune response.

MAP kinase signal-integrating kinase 2 (MNK2)

Target Gene

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				[1]
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 contributes to regeneration.

Melanoma-associated antigen D1 (MAGED1)

Target Gene

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		[53]
Responsed Disease	Pulmonary hypertension [ICD-11: BB01]
Target Regulation	Up regulation
In-vitro Model	PASMC cell line (Pulmonary artery smooth muscle cell)
In-vivo Model	SMC-specific TWIST1-deficient mice were generated by crossing TWIST1^flox/flox mice with animals expressing Sm22-Cre (smooth muscle protein 22-Cre). Deletion of TWIST1 in SMCs was confirmed by histology and Western blot.
Response Summary	YTHDF1 promotes PASMC proliferation and pulmonary hypertension by enhancing Melanoma-associated antigen D1 (MAGED1) translation.

Mutated in multiple advanced cancers 1 (PTEN)

Target Gene

Renal cell carcinoma [ICD-11: 2C90]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[54]
Responsed Disease	Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway	hsa04151
Response Summary	Upregulation of METTL14 inhibited ccRCC cells proliferation and migration in vitro. Overexpression of METTL14 increased the m6A enrichment of Mutated in multiple advanced cancers 1 (PTEN), and promoted Pten expression. METTL14-enhanced Pten mRNA stability was dependent on YTHDF1.

Acute ischemic stroke [ICD-11: 8B11]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[55]
Responsed Disease	Acute ischemic stroke [ICD-11: 8B11]
Target Regulation	Up regulation
In-vitro Model	PC12	Rat adrenal gland pheochromocytoma	Rattus norvegicus	CVCL_0481

Nuclear factor erythroid 2-related factor 2 (NFE2L2)

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[7]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
Pathway Response	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 10⁶ p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nuclear factor erythroid 2-related factor 2 (NFE2L2)-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[57]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Up regulation
In-vitro Model	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	J82	Bladder carcinoma	Homo sapiens	CVCL_0359
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783

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

Target Gene

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				[58]
Responsed Disease	Idiopathic pulmonary fibrosis [ICD-11: CB03.4]
Target Regulation	Up regulation
In-vitro Model	WI-38	Normal	Homo sapiens	CVCL_0579
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Animals were bred and housed in the pathogen-free facility of the Laboratory Animal Center of Shanghai General Hospital (Shanghai, China). All lungs were collected 4 weeks after BLM treatment for histology and further study. Lung microsections (5 uM) were applied to Masson's trichrome and Sirius red staining to visualize fibrotic lesions.
Response Summary	Lowering m6A levels through silencing METTL3 suppresses the FMT process in vitro and in vivo. m6A modification regulates EMT by modulating the translation of Potassium voltage-gated channel subfamily H member 6 (KCNH6) mRNA in a YTHDF1-dependent manner. Manipulation of m6A modification through targeting METTL3 becomes a promising strategy for the treatment of idiopathic pulmonary fibrosis.

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

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[9]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Pathway Response	p53 signaling pathway	hsa04115
	Central carbon metabolism in cancer	hsa05230
	PD-L1 expression and PD-1 checkpoint pathway in cancer	hsa05235
Response Summary	This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher Programmed cell death 1 ligand 1 (CD274/PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, E2 transcription Factor (E2F) targets were significantly enriched.

Protocadherin Fat 4 (FAT4)

Target Gene

Melanoma of uvea [ICD-11: 2D0Y]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[59]
Responsed Disease	Melanoma of uvea [ICD-11: 2D0Y]
Target Regulation	Up regulation
In-vitro Model	Mel290	Uveal melanoma	Homo sapiens	CVCL_C304
	OMM2.3	Uveal melanoma	Homo sapiens	CVCL_C306
	OMM-1	Uveal melanoma	Homo sapiens	CVCL_6939
	CRMM-1	Conjunctival melanoma	Homo sapiens	CVCL_M593
	CRMM-2	Conjunctival melanoma	Homo sapiens	CVCL_M594
	CM2005.1	Conjunctival melanoma	Homo sapiens	CVCL_M592
	MuM-2B	Uveal melanoma	Homo sapiens	CVCL_3447
	ARPE-19	Normal	Homo sapiens	CVCL_0145
	A-375	Amelanotic melanoma	Homo sapiens	CVCL_0132
	SK-MEL-28	Cutaneous melanoma	Homo sapiens	CVCL_0526
	PIG1	Normal	Homo sapiens	CVCL_S410

Rho GTPase activating protein 5 (ARHGAP5)

Target Gene

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[60]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
In-vivo Model	Roughly 1 × 10⁷ of MCF-7 or MDA-MB-231 cells stably transfected with ADAR1 sgRNA or Ctrl sgRNA (as described above) were injected subcutaneously into the thighs of the female athymic nude mice (5 weeks old, 17-18 g, three mice per group). Tumor growth was measured by measuring the width (W) and length (L) with calipers, and the volume (V) of the tumor was figured using the criterion V = (W2 × L)/2. At 43 days after injection, the mice were euthanized and tumors were removed and weighed. The tumor samples were further analyzed with IHC and Western blot assay. The animal studies were performed according to the institutional ethics guidelines for animal experiments and approved by the Chongqing Medical University Animal Care and Use Committee.

Signal transducer and activator of transcription 5A (STAT5A)

Target Gene

Acute ischemic stroke [ICD-11: 8B11]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[61]
Responsed Disease	Acute ischemic stroke [ICD-11: 8B11]
Target Regulation	Down regulation
In-vitro Model	HT22	Normal	Mus musculus	CVCL_0321

SRSF protein kinase 2 (SRPK2)

Target Gene

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[62]
Responsed Disease	Gastric cancer [ICD-11: 2B72]

Staphylococcal nuclease domain-containing protein 1 (SND1)

Target Gene

Nasal-type natural killer/T-cell lymphoma [ICD-11: XH3400]

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	Nasal-type natural killer/T-cell lymphoma [ICD-11: XH3400]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	NK-92	Natural killer cell lymphoblastic leukemia/lymphoma	Homo sapiens	CVCL_2142
	YTS	Lymphoblastic leukemia/lymphoma	Homo sapiens	CVCL_D324
	SNT-8	Nasal type extranodal NK/T-cell lymphoma	Homo sapiens	CVCL_A677
	SNK-6	Nasal type extranodal NK/T-cell lymphoma	Homo sapiens	CVCL_A673
In-vivo Model	A total of 32 nude mice were randomly divided into four groups with eight mice in each group. Nude mice were subcutaneously injected with 2 × 10⁶ cells (suspended in 100 μl of PBS) transfected with NC shRNA or SND1 shRNA into the back flank of mice. In DDP administration group, DDP (3 mg/kg per week for 2 weeks) was intraperitoneally injected into mice every 3 days. The control group received 200 μl of 0.1% DMSO. The tumor volume was measured every week for a total of 4 weeks. The mice were sacrificed after 4 weeks, then the tumors were harvested for weight measurement and other analysis. The tumor volume (mm3) was estimated with the formula (0.5 × length × width2).

Stearoyl-CoA desaturase (SCD)

Target Gene

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

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[64]
Responsed Disease	Nonalcoholic fatty liver disease [ICD-11: DB92.Z]
Target Regulation	Up regulation

Thrombospondin-1 (THBS1)

Target Gene

Acute pericarditis [ICD-11: BB20]

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	Acute pericarditis [ICD-11: BB20.2]
Target Regulation	Up regulation
In-vitro Model	MC3T3-E1	Normal	Mus musculus	CVCL_0409

Tissue factor pathway inhibitor 2 (TFPI-2)

Target Gene

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[66]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Up regulation
Cell Process	Cell growth
	cell migration
	cell invasion
Response Summary	Knockdown of FTO increases m6A methylation of Tissue factor pathway inhibitor 2 (TFPI-2) mRNA in PC cells, thereby increasing mRNA stability via the m6A reader YTHDF1.

Transcription factor p65 (RELA)

Target Gene

Acute ischemic stroke [ICD-11: 8B11]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[67]
Responsed Disease	Acute ischemic stroke [ICD-11: 8B11]
Target Regulation	Up regulation
In-vitro Model	BV-2	Normal	Mus musculus	CVCL_0182

Transcriptional repressor protein YY1 (YY1)

Target Gene

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[68]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
In-vitro Model	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	GES-1	Normal	Homo sapiens	CVCL_EQ22
In-vivo Model	Five-week-old male BALB/c nude mice were used for tumor growth studies in vivo. Briefly, AGS cells were subcutaneously injected into the dorsal side of mice blindly and randomly (n = 5 per group).

Tumor necrosis factor (TNF/TNF-alpha)

Target Gene

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				[25]
Responsed Disease	B-cell lymphomas [ICD-11: 2A86]
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell proliferation and metastasis
	Cell apoptosis
In-vitro Model	ATDC-5	Mouse teratocarcinoma	Mus musculus	CVCL_3894
In-vivo Model	For MIA + SAH control, S-adenosylhomocysteine (SAH), Mettl3 inhibitor (10 mg/kg) (MCE, NJ, USA) was injected intraperitoneally before MIA injection and maintained twice a week until mice were sacrificed.
Response Summary	Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) induced temporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by Tumor necrosis factor (TNF/TNF-alpha) stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Bcl2 signal axis which provides promising therapeutic strategy for temporomandibular joint osteoarthritis.

Dentofacial anomalies [ICD-11: DA0E]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[25]
Responsed Disease	Temporomandibular joint disorders [ICD-11: DA0E.8]
Target Regulation	Up regulation
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell proliferation and metastasis
	Cell apoptosis
In-vitro Model	ATDC-5	Mouse teratocarcinoma	Mus musculus	CVCL_3894
In-vivo Model	For MIA + SAH control, S-adenosylhomocysteine (SAH), Mettl3 inhibitor (10 mg/kg) (MCE, NJ, USA) was injected intraperitoneally before MIA injection and maintained twice a week until mice were sacrificed.
Response Summary	Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) induced temporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by Tumor necrosis factor (TNF/TNF-alpha) stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Bcl2 signal axis which provides promising therapeutic strategy for temporomandibular joint osteoarthritis.

Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)

Target Gene

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[4]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib	Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), ATG12, and ATG16L1.

Ubiquitin-like protein ATG12 (ATG12)

Target Gene

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[4]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib	Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, ATG7, Ubiquitin-like protein ATG12 (ATG12), and ATG16L1.

Ubiquitin-like-conjugating enzyme ATG3 (ATG3)

Target Gene

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[4]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib	Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including Ubiquitin-like-conjugating enzyme ATG3 (ATG3), ATG5, ATG7, ATG12, and ATG16L1.

Zinc finger protein SNAI1 (SNAI1)

Target Gene

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[69]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
	MKN7	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_1417
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
	HEK293T	Normal	Homo sapiens	CVCL_0063
	GES-1	Normal	Homo sapiens	CVCL_EQ22
In-vivo Model	To establish a murine subcutaneous tumor model, sh-PLAGL2 or sh-PLAGL2 + oe-Snail HGC-27 stable transfected HGC-27 cells (5 × 10⁶ cells/kg) subcutaneously to the right of the dorsal midline of mice (n = 6 for each).

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				[70]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
In-vivo Model	All animal experiments complied with Zhongshan School of Medicine Policy on Care and Use of Laboratory Animals. For subcutaneous transplanted model, sh-control and sh-METTL3 Huh7 cells (5 × 10⁶ per mouse, n = 5 for each group) were diluted in 200 uL of PBS + 200 uL Matrigel (BD Biosciences) and subcutaneously injected into immunodeficient female mice to investigate tumor growth.
Response Summary	The upregulation of METTL3 and YTHDF1 act as adverse prognosis factors for overall survival (OS) rate of liver cancer patients. m6A-sequencing and functional studies confirm that Zinc finger protein SNAI1 (SNAI1), a key transcription factor of EMT, is involved in m6A-regulated EMT.

hsa-miR-1914-3p

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[14]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 10⁶ lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-hsa-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.

Anillin (ANLN)

Target Gene

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[71]
Responsed Disease	Liver hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	BEL-7402	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
	HUVEC-C	Normal	Homo sapiens	CVCL_2959
	RAW 264.7	Mouse leukemia	Mus musculus	CVCL_0493
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
In-vivo Model	Using a 100 μl Hamilton Microliter syringe, all the groups of 1 × 10⁷ luciferase-labeled Huh-7 cells in 50 μl 1 x phosphate-buffered saline (PBS) was injected intracardially in the left ventricle of nu/nu, female 4-6-week-old nude mice.

Bone morphogenetic protein 8B (BMP8B)

Target Gene

Obesity [ICD-11: 5B81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[72]
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulation	Up regulation
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Mice were intraperitoneally injected with CL316,243(Sigma) at 1 mg/kg/day for seven consecutive days. To exclude the BAT function, interscapular BAT was surgically removed37,38. The OCR of adipose tissues was performed using Clark-type oxygen electrodes (Strathkelvin Instruments).

cAMP-responsive element modulator (CREM)

Target Gene

Cognitive disorders [ICD-11: 6E0Z]

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	Cognitive disorders [ICD-11: 6E0Z]
Target Regulation	Up regulation
In-vivo Model	40 male Sprague Dawley (SD) rats (7-week-old) were obtained from SJA LABORATORY Animal Co, Ltd. (Hunan, China). After acclimation for 1 week, rats were randomly divided into four groups: the sham group, the sevoflurane group, the sevoflurane + Ad-NC group and the sevoflurane + Ad-YTHDF1 group, with ten animals in each group. Rats in sevoflurane groups were inhaled with 2.2% sevoflurane in the anesthetizing chamber at a flow rate of 1 L per minute for 6 h, and rats in the sham group were inhaled with 40% oxygen. The Ad-NC and Ad-YTHDF1 were constructed by GenePharma (Shanghai, China). Rats in the sevoflurane + Ad-NC group and the sevoflurane + Ad-YTHDF1 group were intracerebroventricularly injected with Ad-NC or Ad-YTHDF1 plasmids (100 μL; 1 × 109 PFU) by a Hamilton microsurgically gauged syringe into the left lateral cerebral ventricles 1 h before sevoflurane anesthesia.

Collagen alpha-1 (COL1A1)

Target Gene

Hepatic fibrosis/cirrhosis [ICD-11: DB93]

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	Hepatic fibrosis/cirrhosis [ICD-11: DB93]
Target Regulation	Up regulation
In-vitro Model	JS1	N.A.	Mus musculus	CVCL_C7PL
In-vivo Model	Following 1 week of adaptive feeding, the mice were randomly divided into CCl4 + siCON and CCl4 + siYTHDF1 groups. Both groups were injected intraperitoneally with 5 ml/kg of 10% carbon tetrachloride (CCl4) twice a week for 4 weeks, to establish liver fibrosis.

Keloid [ICD-11: EE60]

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	Keloid [ICD-11: EE60]
Target Regulation	Up regulation
Cell Process	mRNA stability
In-vitro Model	CHSE-EC	N.A.	Oncorhynchus tshawytscha	CVCL_DG46
In-vivo Model	Six- to eight-week-old C57BL/6 mice were purchased from Cyagen Biosciences, Inc. (Cyagen, Suzhou, China). Alkbh3-/- C57BL/6 mice were generated via the CRISPR/Cas9 system. Single-guide RNAs (sgRNAs) were designed to target exons 3 to 5 of Alkbh3 and were coinjected with Cas9 into the zygotes. The pups obtained were genotyped by PCR. After genotyping, the F0 mice were subjected to serial mating to generate homozygous mutant offspring.

Collagen alpha-2(I) chain (COL1A2)

Target Gene

Hepatic fibrosis/cirrhosis [ICD-11: DB93]

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	Hepatic fibrosis/cirrhosis [ICD-11: DB93]
Target Regulation	Up regulation
In-vitro Model	JS1	N.A.	Mus musculus	CVCL_C7PL
In-vivo Model	Following 1 week of adaptive feeding, the mice were randomly divided into CCl4 + siCON and CCl4 + siYTHDF1 groups. Both groups were injected intraperitoneally with 5 ml/kg of 10% carbon tetrachloride (CCl4) twice a week for 4 weeks, to establish liver fibrosis.

Collagen alpha-2(V) chain (COL5A2)

Target Gene

Hepatic fibrosis/cirrhosis [ICD-11: DB93]

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	Hepatic fibrosis/cirrhosis [ICD-11: DB93]
Target Regulation	Up regulation
In-vitro Model	JS1	N.A.	Mus musculus	CVCL_C7PL
In-vivo Model	Following 1 week of adaptive feeding, the mice were randomly divided into CCl4 + siCON and CCl4 + siYTHDF1 groups. Both groups were injected intraperitoneally with 5 ml/kg of 10% carbon tetrachloride (CCl4) twice a week for 4 weeks, to establish liver fibrosis.

Collagen alpha-2(VI) chain (COL6A2)

Target Gene

Hepatic fibrosis/cirrhosis [ICD-11: DB93]

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	Hepatic fibrosis/cirrhosis [ICD-11: DB93]
Target Regulation	Up regulation
In-vitro Model	JS1	N.A.	Mus musculus	CVCL_C7PL
In-vivo Model	Following 1 week of adaptive feeding, the mice were randomly divided into CCl4 + siCON and CCl4 + siYTHDF1 groups. Both groups were injected intraperitoneally with 5 ml/kg of 10% carbon tetrachloride (CCl4) twice a week for 4 weeks, to establish liver fibrosis.

Cysteine methyltransferase DNMT3A (DNMT3A)

Target Gene

Alzheimer disease [ICD-11: 8A20]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[76]
Responsed Disease	Alzheimer disease [ICD-11: 8A20]
Target Regulation	Up regulation
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063

Dickkopf-related protein 3 (DKK3)

Target Gene

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				[77]
Responsed Disease	Diabetic nephropathy [ICD-11: GB61.Z]
In-vitro Model	HK-2 [Human kidney]	Normal	Homo sapiens	CVCL_0302
In-vivo Model	Female mice (8 weeks old, 20-25 g) on a C57BL/6J background were fasted for 12 h but were allowed to drink water freely. They were then injected intraperitoneally with 50 mg/kg body weight of freshly dissolved STZ in sterile PBS for four consecutive days. Mice were given sterile PBS alone in the same way as an untreated control. The mice's blood glucose levels were assessed two weeks after their most recent treatment. Mice that exhibited glucose levels greater than 202 mg/dL were classified as successful hyperglycemic models and were utilized in subsequent studies. Five months after the final dose of STZ, the mice were euthanized, and the renal tissues were collected for pathological examination to confirm the successful establishment of the model of diabetes nephropathy induced by hyperglycemia. All animal experiments were performed according to the guidelines of the Institutional Animal Care and Use Committee at the China Pharmaceutical University. Isoflurane was used to anesthetize mice.

Discoidin domain-containing receptor 2 (DDR2)

Target Gene

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[78]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Target Regulation	Up regulation
In-vitro Model	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vivo Model	BALB nude mice were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. SKOV3 cells were transfected with sh-METTL3, sh-DDR2, DDR2 over-expression plasmid (oe-DDR2) or negative control. About one week later, the above SKOV3 cells were digested into single cells and subcutaneously injected to nude mice in different groups. After a duration of 4 weeks, the mice were euthanized by intraperitoneal injection of pentobarbital at a dosage 120 mg/kg. Finally, the subcutaneous tumors were removed to measure the size and volume (calculated according to volume = L (longest diameter) x W2 (shorter diameter)/2).

Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 2 (RPN2)

Target Gene

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[79]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Responsed Drug	Cisplatin		Approved	Drug Info
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Pathway Response	mTOR signaling pathway			hsa04150
In-vitro Model	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783

E3 ubiquitin-protein ligase TRIM68 (TRIM68)

Target Gene

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[80]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Up regulation
In-vitro Model	RWPE-2	N.A.	Homo sapiens	CVCL_3792
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
In-vivo Model	Cells (si-NC group, si-YTHDF1 group, si-TRIM68 group, si-YTHDF1 + OE-TRIM68 group) were digested with 0.25% trypsin, and fetal bovine serum was added to prevent excessive digestion. After centrifugation at 1000 rpm for 5 min, cells were collected and suspended with culture medium without serum, and cell density was adjusted to 5 × 10⁷ cells/ml. SPF male BALB/c-nu nude mice (n = 20) were used in this study. Tumor cells (100 μl) were inoculated subcutaneously in the axils of the right forelimbs of mice. After the injection, the mental state, activity, diet, urine and feces of the nude mice were observed regularly every day. The body weight was measured weekly with an electronic balance, and the diameters of subcutaneous graft were measured weekly with vernier caliper. After the tumor grew to about 40 mm3, the nude mice were given flutamine (100 mg/kg; continuous administration for 1 week). The subcutaneous graft tumor volume V (mm3) = longest tumor diameter (mm) × shortest tumor diameter (mm) × 0.5. According to the tumor volume obtained, the growth curve of transplanted tumor was plotted. Five weeks later, the mice were weighed, and sacrificed by cervical dislocation method. The tumor was separated and rinsed with sterile PBS, and then weighed. After weighing, whole blood was taken to separate serum, and tumor tissue was taken. One part was fixed in 4% paraformaldehyde solution, and the other part was stored at -80 °C.

Fibronectin (FN1)

Target Gene

Keloid [ICD-11: EE60]

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	Keloid [ICD-11: EE60]
Target Regulation	Up regulation
Cell Process	mRNA stability
In-vitro Model	CHSE-EC	N.A.	Oncorhynchus tshawytscha	CVCL_DG46
In-vivo Model	Six- to eight-week-old C57BL/6 mice were purchased from Cyagen Biosciences, Inc. (Cyagen, Suzhou, China). Alkbh3-/- C57BL/6 mice were generated via the CRISPR/Cas9 system. Single-guide RNAs (sgRNAs) were designed to target exons 3 to 5 of Alkbh3 and were coinjected with Cas9 into the zygotes. The pups obtained were genotyped by PCR. After genotyping, the F0 mice were subjected to serial mating to generate homozygous mutant offspring.

G1/S-specific cyclin-E2 (CCNE2)

Target Gene

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				[81]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Responsed Drug	Tegaserod		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
In-vitro Model	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064

Glucose-6-phosphate exchanger SLC37A2 (SLC37A2)

Target Gene

Inflammatory bowel disease [ICD-11: DD7Z]

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	Inflammatory bowel disease [ICD-11: DD7Z]
In-vitro Model	RAW 264.7	Mouse leukemia	Mus musculus	CVCL_0493
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
In-vivo Model	Mice were randomly allocated into three groups (n = 5/group): the negative control (NEG) group, the DSS-induced colitis (DSS) group, and the hucMSC-Ex-treated colitis (hucMSC-Ex) group. Mice in the NEG group were fed autoclaved water during the experiment, while mice in the DSS and hucMSC-Ex groups were fed autoclaved water containing 3% DSS (MP Biomedicals, USA). A total of 1 mg of hucMSC-Ex was administered by caudal vein to mice in the hucMSC-Ex group on the 3rd, 6th, and 9th day of modeling, while mice in other groups were injected with PBS. All mice were sacrificed when severe hematochezia and weight loss were observed in the DSS group. The disease progression of mice in the different groups was evaluated by weight change, DAI score, colorectal length, and weight ratio. After the mice were sacrificed, the general view of the spleen and colorectum of the mice was observed. The colorectal mucosa and spleen tissues of the mice in each group were separated, and RNA and protein of the tissues were extracted for subsequent experiments.

Glucose-induced degradation protein 8 homolog (GID8)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[83]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	NCM460	Normal	Homo sapiens	CVCL_0460
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Sh-GID8 stable cells (2 × 10⁶) were inoculated subcutaneously into the left axilla of athymic nude mice (n = 5 mice/group). Every three days, the tumor's size was measured with a digital caliper, and its volume was computed using the following formula: tumor volume (mm3) = length × width × width × 0.52. When the subcutaneous tumor reached approximately 50-100 mm3, glutamine (75 mg/kg) [13] or PBS was injected intratumorally every day. Tumors were collected for TUNEL staining or other analysis when tumor volumes reached the humane endpoint. For the metastasis model, the constructed HCT116 cells (2 × 10⁶) with stable YTHDF1 or GID8 knockdown were injected into nude mice through the tail vein (n = 4 or n = 5 mice/group). Two months later, all the mice were sacrificed to observe tumor metastasis in the lungs.

Glycogen phosphorylase, brain form (PYGB)

Target Gene

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[84]
Responsed Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
In-vitro Model	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	HPDE	Normal	Homo sapiens	CVCL_4376
In-vivo Model	Six BALB/c nude mice (male, 4 weeks) were randomly divided into 2 groups and inoculated with BXPC-3 cells (1 × 10⁶) transfected with shPYGB or shNC by subcutaneous injection. Tumor volume was recorded every 7 days and mice were sacrificed after 6 weeks. To evaluate metastasis in vivo, transfected cells (5 × 10⁶) were injected into nude mice through the tail vein.

GTPase HRas (HRAS)

Target Gene

Soft tissue sarcoma [ICD-11: XH4UM7]

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	Soft tissue sarcoma [ICD-11: XH4UM7]
Target Regulation	Up regulation
In-vitro Model	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	769-P	Renal cell carcinoma	Homo sapiens	CVCL_1050
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
In-vivo Model	A total of 5637 cells with ectopic expression of dm6ACRISPR systems were injected subcutaneously (1 × 10⁷ cells/inoculum) into the flanks of 5-wk-old nude mice (Shanghai Model Organisms Center). Tumor formation/growth was assessed until the experimental endpoint, and tumor volume was calculated by the formula: (width)2 × length/2. For tail vein injection, 5637 cells with ectopic expression of dm6ACRISPR systems (5 × 10⁶ cells/0.1 mL PBS) were injected into the lateral tail vein of 5-wk-old nude mice.

Histone-lysine N-methyltransferase NSD2 (NSD2)

Target Gene

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	Diabetic nephropathy [ICD-11: GB61.Z]
Target Regulation	Up regulation

Homeobox protein DLX-3 (DLX3)

Target Gene

Structural developmental anomalies of teeth and periodontal tissues [ICD-11: LA30]

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	Structural developmental anomalies of teeth and periodontal tissues [ICD-11: LA30.0]

Insulin-like growth factor-binding protein 4 (IGFBP4)

Target Gene

Endometrial cancer [ICD-11: 2C76]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[88]
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Pathway Response	PI3K-Akt signaling pathway			hsa04151
	NF-kappa B signaling pathway			hsa04064
In-vitro Model	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293
In-vivo Model	Ten specific pathogen-free (SPF) BALB/c nude mice (4-6 weeks old, 16 ± 2 g) were purchased from Shanghai Experimental Animal Center, Chinese Academy of Sciences. All experimental animals were kept in a SPF-level aseptic layer at 22-26 °C and 55 ± 5% humidity. Nude mice were randomly divided into sh-NC and sh-METTL3 groups, and these mice were anesthetized by intraperitoneal injection of pentobarbital sodium (60 mg/kg). After anesthesia, the right back skin of the nude mice was disinfected with conventional iodine. The mice in the sh-NC group were injected with 0.2 mL HEC-1-A cell suspension (1 × 10⁶), and those in the sh-METTL3 group were injected with an equal volume of HEC-1-A cells that were stably transfected with sh-METTL3. The injector was slowly withdrawn, and the injection site was pressed for about 10 s to prevent an outflow of cell suspension. Three weeks later, the nude mice were euthanized by cervical dislocation, and subcutaneous tumors were separated and weighted. Tumor volume was measured as follows: tumor volume = 1/2 × length × width2.

Lactadherin (MFGE8)

Target Gene

Acute liver failure [ICD-11: DB91]

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	Acute liver failure [ICD-11: DB91]
Target Regulation	Up regulation

Long intergenic non-protein coding RNA 901 (LINC00901)

Target Gene

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[90]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Down regulation
In-vitro Model	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
In-vivo Model	Nude (nu/nu) mice (4-5 weeks old) were purchased from Harlan Laboratories (Indianapolis, IN, USA). All animal studies were conducted in accordance with NIH animal use guidelines and a protocol approved by the UMMC Animal Care Committee. MIA PaCa-2 cells with LINC00901 overexpression or vector control (pCDH); LINC00901 KO or vector control (LCV2-m) at the exponential stage were harvested and mixed with 50% matrigel, and then injected into mice (2.5 million cells/spot) s.c. as described previously.21 Tumor growth was measured every 4 days, starting 2 weeks after injection of tumor cells.

M-phase inducer phosphatase 1 (CDC25A)

Target Gene

Traumatic brain injury induced by controlled cortical impact injury [ICD-11: NA07]

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	Traumatic brain injury induced by controlled cortical impact injury [ICD-11: NA07]
Target Regulation	Up regulation
In-vitro Model	HT22	Normal	Mus musculus	CVCL_0321
In-vivo Model	A total of twenty-seven adult specific-pathogen-free C57BL/6 mice (male, 10 weeks old, 22-25 g) were obtained from the Animal Center of Xi'an JiaoTong University (Xi'an, China). Mice were housed in a standard environment of 22 ± 0.5°C, 70% humidity with a 12-h light/dark cycle and free access to food and water.

Malignant T-cell-amplified sequence 1 (MCT1)

Target Gene

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[92]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
In-vitro Model	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	HaCaT	Normal	Homo sapiens	CVCL_0038

Methyl-CpG-binding protein 2 (MECP2)

Target Gene

Vascular disorders of the liver [ICD-11: DB98]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[93]
Responsed Disease	Vascular disorders of the liver [ICD-11: DB98.8]
Target Regulation	Up regulation

Neuronal regeneration-related protein (NREP)

Target Gene

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				[94]
Responsed Disease	Pulmonary Fibrosis [ICD-11: CB03.4]
Target Regulation	Up regulation
In-vitro Model	MLE-12	N.A.	Mus musculus	CVCL_3751
In-vivo Model	C57BL/6J mice (6-8 weeks old), purchased from Shanghai Slac Laboratory Animal Co., Ltd (Shanghai, China), were exposed to 0, 10, or 20 ppm NaAsO2 (Sigma, Japan) in drinking water for 6 months [23]. The arsenite concentration in high arsenic groundwater of Northern China is approximately 2 ppm, and the residents are mainly exposed to arsenite via drinking the water from artesian wells [51]. The dose of 20 ppm used in the present study was calculated according to factor (10) for animal-to-human extrapolation. Therefore, the arsenite concentrations used in our animal experiments are related to the human exposure level. As a positive control for pulmonary fibrosis, C57BL/6J mice were injected intraperitoneally with bleomycin (35 mg/kg) (Solarbio, China) twice weekly for 8 weeks. To downregulate, specifically, the levels of YTHDF1 in lung tissues, As-IPF AAV9-SP-Cp-shYTHDF1/AAV9-NC (Shanghai Genechem Co., Ltd, China) was intravenously injected at the 5th month of exposure of 20 ppm NaAsO2. Mice were housed on a 12-hour/12-hour light/dark cycle with free access to normal food.

Oxidized low-density lipoprotein receptor 1 (OLR1)

Target Gene

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[95]
Responsed Disease	Glioma [ICD-11: 2A00.0]
Responsed Drug	Temozolomide		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	U-343MG	Glioblastoma	Homo sapiens	CVCL_S471
In-vitro Model	U-251MG	Astrocytoma	Homo sapiens	CVCL_0021

Pappalysin-1 (PAPPA)

Target Gene

Endometrial cancer [ICD-11: 2C76]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[88]
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Pathway Response	PI3K-Akt signaling pathway			hsa04151
	NF-kappa B signaling pathway			hsa04064
In-vitro Model	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293
In-vivo Model	Ten specific pathogen-free (SPF) BALB/c nude mice (4-6 weeks old, 16 ± 2 g) were purchased from Shanghai Experimental Animal Center, Chinese Academy of Sciences. All experimental animals were kept in a SPF-level aseptic layer at 22-26 °C and 55 ± 5% humidity. Nude mice were randomly divided into sh-NC and sh-METTL3 groups, and these mice were anesthetized by intraperitoneal injection of pentobarbital sodium (60 mg/kg). After anesthesia, the right back skin of the nude mice was disinfected with conventional iodine. The mice in the sh-NC group were injected with 0.2 mL HEC-1-A cell suspension (1 × 10⁶), and those in the sh-METTL3 group were injected with an equal volume of HEC-1-A cells that were stably transfected with sh-METTL3. The injector was slowly withdrawn, and the injection site was pressed for about 10 s to prevent an outflow of cell suspension. Three weeks later, the nude mice were euthanized by cervical dislocation, and subcutaneous tumors were separated and weighted. Tumor volume was measured as follows: tumor volume = 1/2 × length × width2.

Phosphoglycerate kinase 1 (PGK1)

Target Gene

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				[96]
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulation	Up regulation
In-vitro Model	HOK	Normal	Hexagrammos otakii	CVCL_YE19
	SCC-9	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1685
	CAL-27	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1107

PR domain zinc finger protein 15 (PRDM15)

Target Gene

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[97]
Responsed Disease	Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
Target Regulation	Up regulation
In-vitro Model	CC-LP-1	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_0205
In-vitro Model	HuCC-T1	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_0324
In-vivo Model	For subcutaneous inoculation, 1 × 10⁶ control or METTL16-depleted CCA cells suspended in 100 μL PBS mixed with matrix gel (BD, 356,234) at 1:1 ratio was injected into the mice's flanks. Tumor sizes were measured at the relevant time intervals. At the end of the study, the mice were euthanized, and the tumors were dissected and weighed. For intrahepatic inoculation, 1 × 10⁶ control or METTL16-depleted CCLP1 cells suspended in 10 μL PBS mixed with matrix gel (BD, 356,234) at a 1:1 ratio was implanted into the livers of NOD-SCID mice. The mice were sacrificed 8 weeks after injection, their livers were surgically dissected, and the liver/body weight ratios were evaluated.

pre-miR-665

Target Gene

Structural developmental anomalies of teeth and periodontal tissues [ICD-11: LA30]

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	Structural developmental anomalies of teeth and periodontal tissues [ICD-11: LA30.0]

Proliferating cell nuclear antigen (PCNA)

Target Gene

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[98]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Down regulation
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
	RWPE-2	N.A.	Homo sapiens	CVCL_3792
In-vivo Model	The mice were kept under standard conditions and provided with care in accordance with established protocols. For the experiment, 1 × 10⁶ DU145 cells with reduced RBM15B expression and corresponding control cells were injected subcutaneously into the right flank of each nude mouse. Tumor length (L) and width (W) were measured weekly, and tumor volume was calculated using the formula: Volume = (W2 × L) / 2. Four weeks following the injections, mice were euthanized by intraperitoneal administration of sodium pentobarbital at a dose of 151 mg/kg. Tumors were then surgically removed and weighed.

Ras-related protein Rab-27B (RAB27B)

Target Gene

Malignant haematopoietic neoplasm [ICD-11: 2B33]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[99]
Responsed Disease	Chronic myeloid leukaemia [ICD-11: 2B33.2]
Responsed Drug	Rucaparib		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
In-vitro Model	KCL-22	Chronic myelogenous leukemia	Homo sapiens	CVCL_2091
In-vivo Model	K562 cells (1 × 10⁶) were suspended in 100 μL of normal saline and the suspension was mixed with an equal volume of Matrigel. This mixture was subcutaneously injected into the right armpit of 4-week-old mice. Tumor size measurements were initiated on the day of inoculation. The tumor size was calculated using the formula: 0.5 × (long diameter) × (short diameter).2 When the tumor volume reached 100 mm3 (± 20%), rucaparib was given via intragastric administration at 50 mg/kg/d.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[99]
Responsed Disease	Chronic myeloid leukaemia [ICD-11: 2B33.2]
Responsed Drug	Imatinib		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
In-vitro Model	KCL-22	Chronic myelogenous leukemia	Homo sapiens	CVCL_2091
In-vivo Model	K562 cells (1 × 10⁶) were suspended in 100 μL of normal saline and the suspension was mixed with an equal volume of Matrigel. This mixture was subcutaneously injected into the right armpit of 4-week-old mice. Tumor size measurements were initiated on the day of inoculation. The tumor size was calculated using the formula: 0.5 × (long diameter) × (short diameter).2 When the tumor volume reached 100 mm3 (± 20%), rucaparib was given via intragastric administration at 50 mg/kg/d.

Receptor-interacting serine/threonine-protein kinase 4 (RIPK4)

Target Gene

Malignant mixed epithelial mesenchymal tumour [ICD-11: 2B5D]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[100]
Responsed Disease	Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	NF-kappa B signaling pathway			hsa04064
In-vitro Model	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vitro Model	A2780	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
In-vivo Model	Animals were purchased from Changzhou Cavens Laboratory Animal Company (Changzhou, China) and maintained under specific pathogen-free (SPF) conditions. All animal experiments were performed in accordance with the guidelines of the Laboratory Animal Health Committee of Jiangsu University. Approximately 1 × 10⁷ cells were injected subcutaneously into the dorsal surface of female BALB/c nude mice (n = 5 for each group, 4 weeks old, 15 ± 2 g). When the xenograft volume reached approximately 60 mm3 (after 1 week), DDP was intraperitoneally injected three times per week for 3 weeks. On Day 28, the mice were sacrificed and the tumors were frozen at -80 °C for follow-up experiments.

Scavenger receptor class B member 1 (SCARB1)

Target Gene

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[101]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
In-vitro Model	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
	NCI-N87	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_1603
In-vivo Model	ShRNA control (empty vector) and sh-H19 were transfected into BGC-823 cells for 24 h. The cells were collected after digested by trypsin. The cells were washed using phosphate buffered saline (PBS) (Gibco, USA) twice and resuspended with PBS before being subcutaneously injected into nude mice.

Serine/threonine-protein kinase B-raf (BRAF)

Target Gene

Atherosclerosis [ICD-11: BD40]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[102]
Responsed Disease	Atherosclerosis [ICD-11: BD40.Z]
Target Regulation	Up regulation
In-vitro Model	RAW 264.7	Mouse leukemia	Mus musculus	CVCL_0493
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063

SH3 domain-binding protein 5 (SH3BP5)

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[103]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulation	Up regulation
In-vitro Model	NCI-H522	Lung adenocarcinoma	Homo sapiens	CVCL_1567
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	WI-38	Normal	Homo sapiens	CVCL_0579
	IMR-90	Normal	Homo sapiens	CVCL_0347

Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3)

Target Gene

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				[104]
Responsed Disease	Osteoporosis [ICD-11: FB83.1]
In-vitro Model	MC3T3-E1	Normal	Mus musculus	CVCL_0409
In-vivo Model	Female C57BL/6 mice, aged eight weeks, were selected for the study. The mice were divided into three groups with six mice per group. After intramuscular anesthesia (xylazine 10 mg/kg, ketamine 100 mg/kg), two groups underwent bilateral ovariectomy (OVX), while the remaining group had a sham operation. Ovariectomized mice were administered weekly intratibial injections of Mettl14 overexpression adenovirus containing at a concentration of 109 plaque-forming unit per injection, for a duration of 8 weeks. The mice were humanely euthanized one week after the final injection, and their tibia were gathered for further analysis. This study was approved by the ethics committee of Tongji University (NO: TJBH00823101). All the experimental methods were carried out in accordance with the approved guidelines. All experimental procedures involving mice were carried out in strict accordance with the recommendations in the ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments).

Toll-like receptor 2 (TLR2)

Target Gene

Hypopharyngeal cancer [ICD-11: 2B6D]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[105]
Responsed Disease	Hypopharyngeal squamous cell carcinoma [ICD-11: 2B6D.0]
Target Regulation	Up regulation
In-vitro Model	FaDu	Hypopharyngeal squamous cell carcinoma	Homo sapiens	CVCL_1218
In-vitro Model	Detroit 562	Pharyngeal squamous cell carcinoma	Homo sapiens	CVCL_1171
In-vivo Model	HPSCC FaDu or Detroit 562 cells (1 × 10⁶ cells) expressing vector control and construct lentiviruses were subcutaneously injected into the right flanks of 4-week-old male nude mice. Tumor diameters and body weight were recorded every 3 days for 1-6 weeks. Detroit 562 and FaDu cells (1 × 10⁶ cells) were subcutaneously injected into the right flanks of 4-week-old male nude mice.

Tubulointerstitial nephritis antigen-like (TINAGL1)

Target Gene

Esophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[106]
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
In-vitro Model	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
In-vitro Model	Eca-109	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
In-vivo Model	1 × 10⁷ cells were injected into the right axillary region of nude mice. After 28 days, the mice were sacrificed and tumors were removed. ESCA cells (2 × 10⁷ cells) were injected into nude mice via the tail vein. After 6 weeks, the mice were sacrificed and the lungs were obtained and fixed with 4% paraformaldehyde. The number of metastatic nodules was counted following H&E staining.

Zinc finger protein RFP (TRIM27)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[107]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547

Unspecific Target Gene

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[108]
Responsed Disease	Glioma [ICD-11: 2A00.0]
In-vitro Model	SHG-44	Astrocytoma	Homo sapiens	CVCL_6728
	U87 (A primary glioblastoma cell line)
In-vivo Model	About 5 × 10⁶ cells transfected with pc-YTHDF1 in SHG-44 cell (si-YTHDF1 in U87 cell) were suspended in 0.1 mL of PBS and injected subcutaneously into nude mice.
Response Summary	m6A RNA methylation regulators play a potential role in the progression of gliomas. Predicted one microRNA, microRNA 346 that regulated and binded to 3'UTR of YTHDF1, which was confirmed by our fluorescent enzyme reporter gene experiment.

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				[109]
Responsed Disease	Colon cancer [ICD-11: 2B90]
Responsed Drug	Cisplatin		Approved	Drug Info
Pathway Response	Metabolic pathways			hsa01100
Cell Process	Glutamine metabolism
In-vitro Model	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT-29	Colon adenocarcinoma	Homo sapiens	CVCL_0320
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	CRL-1790 (The normal colon epithelial cell line CRL-1790, were purchased from the American Type Culture Collection (ATCC).)
In-vivo Model	Mice were injected subcutaneously with LoVo (1 × 10⁶) cells, which were stably transfected with the control shRNA or YTHDF1 shRNA.
Response Summary	YTHDF1-promoted cisplatin resistance, contributing to overcoming chemoresistant colon cancers.

Colorectal cancer [ICD-11: 2B91]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[110]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Fluorouracil		Approved	Drug Info
Cell Process	Cells proliferation
	Cells migration
	Cells invasion
In-vitro Model	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	KM12-SM	Colon carcinoma	Homo sapiens	CVCL_9548
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	The knockdown of YTHDF1 resulted in the suppression of cancer proliferation and sensitization to the exposure of anticancer drugs such as fluorouracil and oxaliplatin. m6A reader Ythdf1 plays a significant role in colorectal cancer progression. An oncogenic transcription factor MYC was associated with YTHDF1 in both expression and chromatin immunoprecipitation data.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[110]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Oxaliplatin		Approved	Drug Info
Cell Process	Cells proliferation
	Cells migration
	Cells invasion
In-vitro Model	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	KM12-SM	Colon carcinoma	Homo sapiens	CVCL_9548
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	The knockdown of YTHDF1 resulted in the suppression of cancer proliferation and sensitization to the exposure of anticancer drugs such as fluorouracil and oxaliplatin. m6A reader Ythdf1 plays a significant role in colorectal cancer progression. An oncogenic transcription factor MYC was associated with YTHDF1 in both expression and chromatin immunoprecipitation data.

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[111]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Responsed Drug	Gemcitabine		Approved	Drug Info
Pathway Response	Adipocytokine signaling pathway			hsa04920

Cell Process	Epithelial-mesenchymal transition
In-vitro Model	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	HDE-CT cell line (A normal human pancreatic cell line)
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
Response Summary	Lasso regression identified a six-m6A-regulator-signature prognostic model (KIAA1429, HNRNPC, METTL3, YTHDF1, IGF2BP2, and IGF2BP3). Gene set enrichment analysis revealed m6A regulators (KIAA1429, HNRNPC, and IGF2BP2) were related to multiple biological behaviors in pancreatic cancer, including adipocytokine signaling, the well vs. poorly differentiated tumor pathway, tumor metastasis pathway, epithelial mesenchymal transition pathway, gemcitabine resistance pathway, and stemness pathway.

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				[112]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Cell Process	Epithelial-mesenchymal transition
Cell Process	Cell apoptosis
In-vitro Model	BEL-7404	Endocervical adenocarcinoma	Homo sapiens	CVCL_6568
	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	MHCC97-L	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4973
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
Response Summary	YTHDF1 promotes the aggressive phenotypes by facilitating epithelial-mesenchymal transition (EMT) and activating AKT/glycogen synthase kinase (GSK)-3-beta/beta-catenin signaling in hepatocellular carcinoma.

Metabolic dysfunction-associated steatotic liver disease [ICD-11: 5C90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[115]
Responsed Disease	Metabolic dysfunction-associated steatotic liver disease [ICD-11: 5C90]
In-vitro Model	AML12	Normal	Mus musculus	CVCL_0140

Alzheimer disease [ICD-11: 8A20]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[116]
Responsed Disease	Alzheimer disease [ICD-11: 8A20]
Cell Process	Oxidative stress
	Cell apoptosis
	Mitochondrial dysfunction
In-vitro Model	CCF-STTG1	Astrocytoma	Homo sapiens	CVCL_1118
Response Summary	Perturbed m6A signaling can be contributing to Alzheimer's disease pathogenesis, likely by compromising astrocyte bioenergetics. MO-I-500, a novel pharmacological inhibitor of FTO, can strongly reduce the adverse effects of STZ. STZ-treated astrocytes expressed significantly higher levels of m6A demethylase FTO and m6A reader YTHDF1.

Acute ischemic stroke [ICD-11: 8B11]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[117]
Responsed Disease	Acute ischemic stroke [ICD-11: 8B11]
In-vivo Model	36 male C57BL/6J mice (20-22 g, 2-month-old) were purchased from SPF (Beijing) biotechnology co., Ltd (Beijing, China) and maintained in the specific pathogen-free (SPF) animal laboratory with a 12/12 h light/dark cycle with free access to food and water. The mice were randomly assigned into six groups (n = 6 per group): (1) sham-operated group (Sham), (2) MCAO 6 h, (3) MCAO 12 h, (4) MCAO 1 d, (5) MCAO 3 d, and (6) MCAO 7 d.

Myasthenia gravis [ICD-11: 8C60]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[118]
Responsed Disease	Myasthenia gravis [ICD-11: 8C60]
Pathway Response	Wnt signaling pathway	hsa04310

Forkhead box protein O3 (FOXO3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shNC AGS		GSE166972
Regulation		logFC: 1.07E+00 p-value: 3.17E-02
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.44E+00	GSE63591

Sorafenib [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[4]
Responsed Disease	Hepatocellular carcinoma	ICD-11: 2C12.02	Disease Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising Forkhead box protein 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 ATG16L1.

Kelch-like ECH-associated protein 1 (KEAP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shControl AGS		GSE159425
Regulation		logFC: 1.01E+00 p-value: 4.73E-09
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.61E+00	GSE63591

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[7]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
Pathway Response	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 10⁶ p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Kelch-like ECH-associated protein 1 (KEAP1)-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.

PR domain zinc finger protein 2 (PRDM2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shNC AGS		GSE166972
Regulation		logFC: 2.20E+00 p-value: 3.42E-04
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.84E+00	GSE63591

Arsenite [Phase 2]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[10]
Responsed Disease	Solid tumour/cancer		ICD-11: 2A00-2F9Z	Disease Info
Target Regulation	Down regulation
Pathway Response	p53 signaling pathway			hsa04115
In-vitro Model	HaCaT	Normal	Homo sapiens	CVCL_0038
Response Summary	METTL3 significantly decreased m6A level, restoring p53 activation and inhibiting cellular transformation phenotypes in the arsenite-transformed cells. m6A downregulated the expression of the positive p53 regulator, PR domain zinc finger protein 2 (PRDM2), through the YTHDF2-promoted decay of PRDM2 mRNAs. m6A upregulated the expression of the negative p53 regulator, YY1 and MDM2 through YTHDF1-stimulated translation of YY1 and MDM2 mRNA. This study further sheds light on the mechanisms of arsenic carcinogenesis via RNA epigenetics.

Transcription factor E2F8 (E2F8)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shControl AGS		GSE159425
Regulation		logFC: -8.62E-01 p-value: 7.08E-04
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.18E+00	GSE63591

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[12]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stability
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	Hs 578T	Invasive breast carcinoma	Homo sapiens	CVCL_0332
In-vivo Model	1×10⁶ MDA-MB-231 cells were resuspended in 100 uL PBS with 50% Matrigel (Corning Costar, USA), and injected into the mammary fat pad of the mice.
Response Summary	In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner.

Doxil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[12]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stability
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	Hs 578T	Invasive breast carcinoma	Homo sapiens	CVCL_0332
In-vivo Model	1×10⁶ MDA-MB-231 cells were resuspended in 100 uL PBS with 50% Matrigel (Corning Costar, USA), and injected into the mammary fat pad of the mice.
Response Summary	In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner.

Olaparib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[12]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Cell Process	RNA stability
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	Hs 578T	Invasive breast carcinoma	Homo sapiens	CVCL_0332
In-vivo Model	1×10⁶ MDA-MB-231 cells were resuspended in 100 uL PBS with 50% Matrigel (Corning Costar, USA), and injected into the mammary fat pad of the mice.
Response Summary	In breast cancer, accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. Transcription factor E2F8 (E2F8) is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner.

Transcriptional coactivator YAP1 (YAP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shNC AGS		GSE166972
Regulation		logFC: 3.89E+00 p-value: 1.09E-02
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.35E+00	GSE63591

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[14]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 10⁶ lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-Transcriptional coactivator YAP1 (YAP1) axis to induce Non-small cell lung cancer drug resistance and metastasis.

Autophagy-related protein 16-1 (ATG16L1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shNC AGS		GSE166972
Regulation		logFC: -1.37E+00 p-value: 3.41E-02
More Results	Click to View More RNA-seq Results

Sorafenib [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[4]
Responsed Disease	Hepatocellular carcinoma	ICD-11: 2C12.02	Disease Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, ATG7, ATG12, and Autophagy-related protein 16-1 (ATG16L1).

Beclin-1 (BECN1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shNC AGS		GSE166972
Regulation		logFC: -1.33E+00 p-value: 2.29E-02
More Results	Click to View More RNA-seq Results

Sorafenib [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[17]
Responsed Disease	Hepatocellular carcinoma	ICD-11: 2C12.02	Disease Info
Target Regulation	Up regulation
Pathway Response	Ferroptosis		hsa04216
	Autophagy		hsa04140
Cell Process	Ferroptosis
	Cell autophagy
In-vitro Model	HSC (Hematopoietic stem cell)
In-vivo Model	VA-Lip-Mettl4-shRNA, VA-Lip-Fto-Plasmid and VA-Lip-Ythdf1-shRNA (0.75 mg/kg) were injected intravenously 3 times a week.
Response Summary	Analyzed the effect of sorafenib on HSC ferroptosis and m6A modification in advanced fibrotic patients with hepatocellular carcinoma receiving sorafenib monotherapy. YTHDF1 promotes Beclin-1 (BECN1) mRNA stability and autophagy activation via recognizing the m6A binding site within BECN1 coding regions.

Cyclin-dependent kinase 2 (CDK2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shControl AGS		GSE159425
Regulation		logFC: -8.20E-01 p-value: 7.96E-07
More Results	Click to View More RNA-seq Results

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[7]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
Pathway Response	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 10⁶ p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of Cyclin-dependent kinase 2 (CDK2), CDK4, p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.

Tripartite motif-containing protein 29 (TRIM29)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1*
Cell Line	AGS cell line	Homo sapiens
Treatment: shYTHDF1 AGS Control: shNC AGS		GSE166972
Regulation		logFC: 2.23E+00 p-value: 1.11E-02
More Results	Click to View More RNA-seq Results

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[23]
Responsed Disease	Ovarian cancer		ICD-11: 2C73	Disease Info
Target Regulation	Up regulation
Cell Process	Ectopic expression
In-vitro Model	A2780	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
In-vitro Model	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vivo Model	The specified number of viable SKOV3/DDP cells and SKOV3/DDP cells with TRIM29 knock down were resuspended in 100 uL PBS, injected subcutaneously under the left and right back of 4-week old nude mice respectively (n = 3 per group).
Response Summary	m6A-YTHDF1-mediated Tripartite motif-containing protein 29 (TRIM29) upregulation facilitates the stem cell-like phenotype of cisplatin-resistant ovarian cancer cells. TRIM29 acts as an oncogene to promote the CSC-like features of cisplatin-resistant ovarian cancer in an m6A-YTHDF1-dependent manner.

Poly [ADP-ribose] polymerase 1 (PARP1)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.06E+00	GSE63591

Oxaliplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[32]
Responsed Disease	Gastric cancer		ICD-11: 2B72	Disease Info
Target Regulation	Up regulation
Pathway Response	Nucleotide excision repair			hsa03420
Pathway Response	Signaling pathways regulating pluripotency of stem cells			hsa04550
Cell Process	RNA stability
Cell Process	Excision repair
In-vitro Model	SNU-719	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_5086
	MKN74	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_2791
	HEK293T	Normal	Homo sapiens	CVCL_0063
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
In-vivo Model	100,000 pLKO and PARP1-sh1 (PT1 and PT2) cells were mixed with matrix gel and inoculate into BALB/C nude mice, respectively. After 25 days, 6 organoid transplanted tumor mice were treated with oxaliplatin (Sellekchem, s1224) twice a week for 4 weeks at a dose of 5 mg/kg.
Response Summary	m6A methyltransferase METTL3 facilitates oxaliplatin resistance in CD133+ gastric cancer stem cells by Promoting PARP1 mRNA stability which increases base excision repair pathway activity. METTTL3 enhances the stability of PARP1 by recruiting Poly [ADP-ribose] polymerase 1 (PARP1) to target the 3'-untranslated Region (3'-UTR) of PARP1 mRNA.

Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF1*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.44E+00	GSE63591

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[14]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 10⁶ lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.

Aldo-keto reductase family 1 member C1 (AKR1C1)

Target Gene

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[7]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Down regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
Pathway Response	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 10⁶ p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nrf2-Aldo-keto reductase family 1 member C1 (AKR1C1) axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.

Autophagy protein 5 (ATG5)

Target Gene

Sorafenib [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[4]
Responsed Disease	Hepatocellular carcinoma	ICD-11: 2C12.02	Disease Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, Autophagy protein 5 (ATG5), ATG7, ATG12, and ATG16L1.

Cellular tumor antigen p53 (TP53/p53)

Target Gene

Arsenite [Phase 2]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[10]
Responsed Disease	Solid tumour/cancer		ICD-11: 2A00-2F9Z	Disease Info
Target Regulation	Down 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.

Cyclin-dependent kinase 4 (CDK4)

Target Gene

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[7]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
Pathway Response	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 10⁶ p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, Cyclin-dependent kinase 4 (CDK4), p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.

Cyclin-dependent kinase inhibitor 1B (CDKN1B/p27)

Target Gene

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[7]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Down regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
Pathway Response	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 10⁶ p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, Cyclin-dependent kinase inhibitor 1B (CDKN1B/p27), and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.

G1/S-specific cyclin-D1 (CCND1)

Target Gene

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[7]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
Pathway Response	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 10⁶ p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and G1/S-specific cyclin-D1 (CCND1), and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.

Nuclear factor erythroid 2-related factor 2 (NFE2L2)

Target Gene

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[7]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Down regulation
Pathway Response	Chemical carcinogenesis - reactive oxygen species			hsa05208
Pathway Response	Cell cycle			hsa04110
Cell Process	Biological regulation
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A549-DDP (Human lung adenocarcinoma is resistant to cisplatin)
	GLC-82	Endocervical adenocarcinoma	Homo sapiens	CVCL_3371
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In-vivo Model	Mice were treated via nasal inhalation of adenovirus carrying Cre recombinase (5 × 10⁶ p.f.u for Ad-Cre, Biowit Inc., Shenzhen, Guangdong), and were then killed at indicated times for gross inspection and histopathological examination.
Response Summary	YTHDF1 deficiency inhibits Non-small cell lung cancer cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, p27, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. Mechanistic studies identified the Keap1-Nuclear factor erythroid 2-related factor 2 (NFE2L2)-AKR1C1 axis as the downstream mediator of YTHDF1. YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment.

Staphylococcal nuclease domain-containing protein 1 (SND1)

Target Gene

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[63]
Responsed Disease	Nasal-type natural killer/T-cell lymphoma		ICD-11: XH3400	Disease Info
Target Regulation	Up regulation
In-vitro Model	NK-92	Natural killer cell lymphoblastic leukemia/lymphoma	Homo sapiens	CVCL_2142
	YTS	Lymphoblastic leukemia/lymphoma	Homo sapiens	CVCL_D324
	SNT-8	Nasal type extranodal NK/T-cell lymphoma	Homo sapiens	CVCL_A677
	SNK-6	Nasal type extranodal NK/T-cell lymphoma	Homo sapiens	CVCL_A673
In-vivo Model	A total of 32 nude mice were randomly divided into four groups with eight mice in each group. Nude mice were subcutaneously injected with 2 × 10⁶ cells (suspended in 100 μl of PBS) transfected with NC shRNA or SND1 shRNA into the back flank of mice. In DDP administration group, DDP (3 mg/kg per week for 2 weeks) was intraperitoneally injected into mice every 3 days. The control group received 200 μl of 0.1% DMSO. The tumor volume was measured every week for a total of 4 weeks. The mice were sacrificed after 4 weeks, then the tumors were harvested for weight measurement and other analysis. The tumor volume (mm3) was estimated with the formula (0.5 × length × width2).

Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)

Target Gene

Sorafenib [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[4]
Responsed Disease	Hepatocellular carcinoma	ICD-11: 2C12.02	Disease Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), ATG12, and ATG16L1.

Ubiquitin-like protein ATG12 (ATG12)

Target Gene

Sorafenib [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[4]
Responsed Disease	Hepatocellular carcinoma	ICD-11: 2C12.02	Disease Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, ATG7, Ubiquitin-like protein ATG12 (ATG12), and ATG16L1.

Ubiquitin-like-conjugating enzyme ATG3 (ATG3)

Target Gene

Sorafenib [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[4]
Responsed Disease	Hepatocellular carcinoma	ICD-11: 2C12.02	Disease Info
Target Regulation	Up regulation
Pathway Response	FoxO signaling pathway		hsa04068
	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including Ubiquitin-like-conjugating enzyme ATG3 (ATG3), ATG5, ATG7, ATG12, and ATG16L1.

hsa-miR-1914-3p

Target Gene

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[14]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Metabolic
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Calu-6	Lung adenocarcinoma	Homo sapiens	CVCL_0236
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H520	Lung squamous cell carcinoma	Homo sapiens	CVCL_1566
In-vivo Model	Mice were injected with 5 × 10⁶ lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Response Summary	METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-hsa-miR-1914-3p-YAP axis to induce Non-small cell lung cancer drug resistance and metastasis.

CREB-binding protein (CREBBP)

Target Gene

PT2385 [Investigative]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene		[75]
Target Regulation	Up regulation

Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 2 (RPN2)

Target Gene

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[79]
Responsed Disease	Bladder cancer		ICD-11: 2C94	Disease Info
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Pathway Response	mTOR signaling pathway			hsa04150
In-vitro Model	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783

G1/S-specific cyclin-E2 (CCNE2)

Target Gene

Tegaserod [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[81]
Responsed Disease	Acute myeloid leukaemia		ICD-11: 2A60	Disease Info
Target Regulation	Up regulation
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
In-vitro Model	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064

Oxidized low-density lipoprotein receptor 1 (OLR1)

Target Gene

Temozolomide [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[95]
Responsed Disease	Glioma		ICD-11: 2A00.0	Disease Info
Target Regulation	Up regulation
In-vitro Model	U-343MG	Glioblastoma	Homo sapiens	CVCL_S471
In-vitro Model	U-251MG	Astrocytoma	Homo sapiens	CVCL_0021

Ras-related protein Rab-27B (RAB27B)

Target Gene

Rucaparib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[99]
Responsed Disease	Chronic myeloid leukaemia		ICD-11: 2B33.2	Disease Info
Target Regulation	Up regulation
In-vitro Model	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
In-vitro Model	KCL-22	Chronic myelogenous leukemia	Homo sapiens	CVCL_2091
In-vivo Model	K562 cells (1 × 10⁶) were suspended in 100 μL of normal saline and the suspension was mixed with an equal volume of Matrigel. This mixture was subcutaneously injected into the right armpit of 4-week-old mice. Tumor size measurements were initiated on the day of inoculation. The tumor size was calculated using the formula: 0.5 × (long diameter) × (short diameter).2 When the tumor volume reached 100 mm3 (± 20%), rucaparib was given via intragastric administration at 50 mg/kg/d.

Imatinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[99]
Responsed Disease	Chronic myeloid leukaemia		ICD-11: 2B33.2	Disease Info
Target Regulation	Up regulation
In-vitro Model	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
In-vitro Model	KCL-22	Chronic myelogenous leukemia	Homo sapiens	CVCL_2091
In-vivo Model	K562 cells (1 × 10⁶) were suspended in 100 μL of normal saline and the suspension was mixed with an equal volume of Matrigel. This mixture was subcutaneously injected into the right armpit of 4-week-old mice. Tumor size measurements were initiated on the day of inoculation. The tumor size was calculated using the formula: 0.5 × (long diameter) × (short diameter).2 When the tumor volume reached 100 mm3 (± 20%), rucaparib was given via intragastric administration at 50 mg/kg/d.

Receptor-interacting serine/threonine-protein kinase 4 (RIPK4)

Target Gene

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[100]
Responsed Disease	Malignant mixed epithelial mesenchymal tumour of ovary		ICD-11: 2B5D.0	Disease Info
Target Regulation	Up regulation
Pathway Response	NF-kappa B signaling pathway			hsa04064
In-vitro Model	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In-vitro Model	A2780	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
In-vivo Model	Animals were purchased from Changzhou Cavens Laboratory Animal Company (Changzhou, China) and maintained under specific pathogen-free (SPF) conditions. All animal experiments were performed in accordance with the guidelines of the Laboratory Animal Health Committee of Jiangsu University. Approximately 1 × 10⁷ cells were injected subcutaneously into the dorsal surface of female BALB/c nude mice (n = 5 for each group, 4 weeks old, 15 ± 2 g). When the xenograft volume reached approximately 60 mm3 (after 1 week), DDP was intraperitoneally injected three times per week for 3 weeks. On Day 28, the mice were sacrificed and the tumors were frozen at -80 °C for follow-up experiments.

Zinc finger protein RFP (TRIM27)

Target Gene

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[107]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Up regulation
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547

Unspecific Target Gene

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[109]
Responsed Disease	Colon cancer		ICD-11: 2B90	Disease Info
Pathway Response	Metabolic pathways			hsa01100
Cell Process	Glutamine metabolism
In-vitro Model	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT-29	Colon adenocarcinoma	Homo sapiens	CVCL_0320
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	CRL-1790 (The normal colon epithelial cell line CRL-1790, were purchased from the American Type Culture Collection (ATCC).)
In-vivo Model	Mice were injected subcutaneously with LoVo (1 × 10⁶) cells, which were stably transfected with the control shRNA or YTHDF1 shRNA.
Response Summary	YTHDF1-promoted cisplatin resistance, contributing to overcoming chemoresistant colon cancers.

Fluorouracil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[110]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Cell Process	Cells proliferation
	Cells migration
	Cells invasion
In-vitro Model	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	KM12-SM	Colon carcinoma	Homo sapiens	CVCL_9548
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	The knockdown of YTHDF1 resulted in the suppression of cancer proliferation and sensitization to the exposure of anticancer drugs such as fluorouracil and oxaliplatin. m6A reader Ythdf1 plays a significant role in colorectal cancer progression. An oncogenic transcription factor MYC was associated with YTHDF1 in both expression and chromatin immunoprecipitation data.

Oxaliplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[110]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Cell Process	Cells proliferation
	Cells migration
	Cells invasion
In-vitro Model	Caco-2	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	KM12-SM	Colon carcinoma	Homo sapiens	CVCL_9548
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	The knockdown of YTHDF1 resulted in the suppression of cancer proliferation and sensitization to the exposure of anticancer drugs such as fluorouracil and oxaliplatin. m6A reader Ythdf1 plays a significant role in colorectal cancer progression. An oncogenic transcription factor MYC was associated with YTHDF1 in both expression and chromatin immunoprecipitation data.

Gemcitabine [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[111]
Responsed Disease	Pancreatic cancer		ICD-11: 2C10	Disease Info
Pathway Response	Adipocytokine signaling pathway			hsa04920

Cell Process	Epithelial-mesenchymal transition
In-vitro Model	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	HDE-CT cell line (A normal human pancreatic cell line)
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
Response Summary	Lasso regression identified a six-m6A-regulator-signature prognostic model (KIAA1429, HNRNPC, METTL3, YTHDF1, IGF2BP2, and IGF2BP3). Gene set enrichment analysis revealed m6A regulators (KIAA1429, HNRNPC, and IGF2BP2) were related to multiple biological behaviors in pancreatic cancer, including adipocytokine signaling, the well vs. poorly differentiated tumor pathway, tumor metastasis pathway, epithelial mesenchymal transition pathway, gemcitabine resistance pathway, and stemness pathway.

Click to View Potential Drug Response of This Regulator

Full List of Crosstalk(s) between m6A Modification and Epigenetic Regulation Related to This Regulator

RNA modification

m6A Target: Collagen alpha-1 (COL1A1)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT00054		Crosstalk Info
Epigenetic Regulator	Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 (ALKBH3)
Regulated Target	Methyltransferase-like protein 3 (METTL3)
Crosstalk relationship	m1A → m6A
Disease	Keloid	Disease Info
Crosstalk ID: M6ACROT00056		Crosstalk Info
Epigenetic Regulator	YTH domain-containing family protein 2 (YTHDF2)
Regulated Target	Methyltransferase-like protein 3 (METTL3)
Crosstalk relationship	m1A → m6A
Disease	Keloid	Disease Info

m6A Target: Fibronectin (FN1)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT00055		Crosstalk Info
Epigenetic Regulator	Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 (ALKBH3)
Regulated Target	Methyltransferase-like protein 3 (METTL3)
Crosstalk relationship	m1A → m6A
Disease	Keloid	Disease Info
Drug	Ocriplasmin	Drug Info
Crosstalk ID: M6ACROT00057		Crosstalk Info
Epigenetic Regulator	YTH domain-containing family protein 2 (YTHDF2)
Regulated Target	Methyltransferase-like protein 3 (METTL3)
Crosstalk relationship	m1A → m6A
Disease	Keloid	Disease Info
Drug	Ocriplasmin	Drug Info

m6A Target: Interferon-inducible protein 4 (ADAR1)

Target Gene

In total 4 item(s) under this m6A target
Crosstalk ID: M6ACROT00060		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	Tankyrase (TNKS)
Crosstalk relationship	m6A → A-to-I
Drug	PMID27841036-Compound-37	Drug Info
Crosstalk ID: M6ACROT00061		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	Tyrosine-protein kinase EIF2AK2 (eIF2AK2/p68)
Crosstalk relationship	m6A → A-to-I
Drug	US9650366, 12	Drug Info
Crosstalk ID: M6ACROT00062		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	Proteasome 20S subunit beta 2 (PSMB2)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00064		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	Cyclin-dependent kinase 2 (CDK2)
Crosstalk relationship	m6A → A-to-I
Disease	Glioblastoma	Disease Info
Drug	PHA848125	Drug Info

m6A Target: Rho GTPase activating protein 5 (ARHGAP5)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT00066		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	Methyltransferase-like protein 3 (METTL3)
Crosstalk relationship	A-to-I → m6A
Disease	Breast cancer	Disease Info

m6A Target: Epidermal growth factor receptor (EGFR)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT00445		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	MicroRNA 214 (MIR214)
Crosstalk relationship	A-to-I → m6A

m6A Target: Transferrin receptor protein 1 (TFRC)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT00452		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	MicroRNA 214 (MIR214)
Crosstalk relationship	A-to-I → m6A

DNA modification

m6A Target: Collagen alpha-1 (COL1A1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02001		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Suppressor of cytokine signaling 3 (SOCS3)
Crosstalk relationship	DNA modification → m6A
Disease	Hepatic fibrosis/cirrhosis	Disease Info

m6A Target: Collagen alpha-2(I) chain (COL1A2)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02002		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Suppressor of cytokine signaling 3 (SOCS3)
Crosstalk relationship	DNA modification → m6A
Disease	Hepatic fibrosis/cirrhosis	Disease Info

m6A Target: Collagen alpha-1 (III) chain (COL3A1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02003		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Suppressor of cytokine signaling 3 (SOCS3)
Crosstalk relationship	DNA modification → m6A
Disease	Hepatic fibrosis/cirrhosis	Disease Info

m6A Target: Collagen alpha-2(V) chain (COL5A2)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02004		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Suppressor of cytokine signaling 3 (SOCS3)
Crosstalk relationship	DNA modification → m6A
Disease	Hepatic fibrosis/cirrhosis	Disease Info

m6A Target: Collagen alpha-2(VI) chain (COL6A2)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02005		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Suppressor of cytokine signaling 3 (SOCS3)
Crosstalk relationship	DNA modification → m6A
Disease	Hepatic fibrosis/cirrhosis	Disease Info

m6A Target: DNA (cytosine-5)-methyltransferase 3B (DNMT3B)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02074		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Crosstalk relationship	m6A → DNA modification
Disease	Gastric cancer	Disease Info

m6A Target: Cysteine methyltransferase DNMT3A (DNMT3A)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02077		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Alpha tubulin acetyltransferase 1 (ATAT1)
Crosstalk relationship	m6A → DNA modification
Disease	Alzheimer disease	Disease Info

m6A Target: Methyl-CpG-binding protein 2 (MECP2)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02108		Crosstalk Info
Epigenetic Regulator	Methyl-CpG-binding protein 2 (MECP2)
Regulated Target	Solute carrier family 31 member 1 (SLC31A1)
Crosstalk relationship	m6A → DNA modification
Disease	Vascular disorders of the liver	Disease Info

Histone modification

m6A Target: Protocadherin Fat 4 (FAT4)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03053		Crosstalk Info
Epigenetic Regulator	Histone Deacetylase (HDAC)
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Melanoma of uvea	Disease Info
Crosstalk ID: M6ACROT03054		Crosstalk Info
Epigenetic Regulator	Histone Deacetylase (HDAC)
Regulated Target	Histone H3 lysine 9 acetylation (H3K9Ac)
Crosstalk relationship	Histone modification → m6A
Disease	Melanoma of uvea	Disease Info

m6A Target: PR domain zinc finger protein 15 (PRDM15)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03070		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Intrahepatic cholangiocarcinoma	Disease Info

m6A Target: Stearoyl-CoA desaturase (SCD)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03135		Crosstalk Info
Epigenetic Regulator	Lactate dehydrogenase A (LDHA)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18lac)
Crosstalk relationship	Histone modification → m6A
Disease	Nonalcoholic fatty liver disease	Disease Info

m6A Target: Histone-lysine N-methyltransferase NSD2 (NSD2)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03210		Crosstalk Info
Epigenetic Regulator	Histone-lysine N-methyltransferase NSD2 (NSD2)
Regulated Target	Histone H3 lysine 36 dimethylation (H3K36me2)
Crosstalk relationship	m6A → Histone modification
Disease	Diabetic nephropathy	Disease Info
Crosstalk ID: M6ACROT03212		Crosstalk Info
Epigenetic Regulator	Histone-lysine N-methyltransferase NSD2 (NSD2)
Regulated Target	Histone H3 lysine 36 trimethylation (H3K36me3)
Crosstalk relationship	m6A → Histone modification
Disease	Diabetic nephropathy	Disease Info

m6A Target: CREB-binding protein (CREBBP)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03218		Crosstalk Info
Epigenetic Regulator	CREB-binding protein (CREBBP)
Crosstalk relationship	m6A → Histone modification
Drug	BHBA	Drug Info

m6A Target: E3 ubiquitin-protein ligase RING2 (RNF2)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03220		Crosstalk Info
Epigenetic Regulator	E3 ubiquitin-protein ligase RING2 (RNF2)
Regulated Target	Histone H2A lysine 119 ubiquitination (H2AK119ub)
Crosstalk relationship	m6A → Histone modification

m6A Target: Dickkopf-related protein 3 (DKK3)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03354		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Diabetic nephropathy	Disease Info
Drug	SETDB1-TTD-IN-1	Drug Info

Non-coding RNA

m6A Target: Microtubule-associated protein tau (TAU)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05087		Crosstalk Info
Epigenetic Regulator	DPPA2 upstream binding RNA (DUBR)
Regulated Target	YTH domain-containing family protein 1 (YTHDF1)
Crosstalk relationship	ncRNA → m6A

m6A Target: Calmodulin-1 (CALM1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05089		Crosstalk Info
Epigenetic Regulator	DPPA2 upstream binding RNA (DUBR)
Regulated Target	YTH domain-containing family protein 1 (YTHDF1)
Crosstalk relationship	ncRNA → m6A

m6A Target: Myc proto-oncogene protein (MYC)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05115		Crosstalk Info
Epigenetic Regulator	DLGAP1 antisense RNA 2 (DLGAP1-AS2)
Regulated Target	YTH domain-containing family protein 1 (YTHDF1)
Crosstalk relationship	ncRNA → m6A
Disease	Non-small cell lung cancer	Disease Info

m6A Target: Hexokinase-2 (HK2)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05116		Crosstalk Info
Epigenetic Regulator	HLA complex P5 (HCP5)
Regulated Target	YTH domain-containing family protein 1 (YTHDF1)
Crosstalk relationship	ncRNA → m6A
Disease	Esophageal Squamous Cell Carcinoma	Disease Info

m6A Target: Scavenger receptor class B member 1 (SCARB1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05117		Crosstalk Info
Epigenetic Regulator	H19 imprinted maternally expressed transcript (H19)
Regulated Target	YTH domain-containing family protein 1 (YTHDF1)
Crosstalk relationship	ncRNA → m6A
Disease	Gastric cancer	Disease Info

m6A Target: Interleukin-18 (IL18)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05191		Crosstalk Info
Epigenetic Regulator	hsa-miR-381
Regulated Target	YTH domain-containing family protein 1 (YTHDF1)
Crosstalk relationship	ncRNA → m6A

m6A Target: Rho GTPase activating protein 5 (ARHGAP5)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05219		Crosstalk Info
Epigenetic Regulator	hsa-miR-532-5p
Regulated Target	Methyltransferase-like protein 3 (METTL3)
Crosstalk relationship	ncRNA → m6A
Disease	Breast cancer	Disease Info

m6A Target: Zinc finger protein SNAI1 (SNAI1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05230		Crosstalk Info
Epigenetic Regulator	hsa-miR-145-5p
Regulated Target	YTH domain-containing family protein 1 (YTHDF1)
Crosstalk relationship	ncRNA → m6A
Disease	Gastric cancer	Disease Info

m6A Target: Transcription factor p65 (RELA)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05263		Crosstalk Info
Epigenetic Regulator	hsa-miR-421-3p
Regulated Target	YTH domain-containing family protein 1 (YTHDF1)
Crosstalk relationship	ncRNA → m6A
Disease	Acute ischemic stroke	Disease Info

m6A Target: Catenin beta-1 (CTNNB1/Beta-catenin)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT05267		Crosstalk Info
Epigenetic Regulator	hsa-miR-136-5p
Regulated Target	YTH domain-containing family protein 1 (YTHDF1)
Crosstalk relationship	ncRNA → m6A
Disease	Colorectal cancer	Disease Info
Crosstalk ID: M6ACROT05335		Crosstalk Info
Epigenetic Regulator	hsa-miR-376c
Regulated Target	YTH domain-containing family protein 1 (YTHDF1)
Crosstalk relationship	ncRNA → m6A
Disease	Non-small cell lung cancer	Disease Info

m6A Target: Rho guanine nucleotide exchange factor 2 (ARHGEF2)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05268		Crosstalk Info
Epigenetic Regulator	hsa-miR-136-5p
Regulated Target	YTH domain-containing family protein 1 (YTHDF1)
Crosstalk relationship	ncRNA → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Zinc finger protein RFP (TRIM27)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05269		Crosstalk Info
Epigenetic Regulator	hsa-miR-136-5p
Regulated Target	YTH domain-containing family protein 1 (YTHDF1)
Crosstalk relationship	ncRNA → m6A
Disease	Colorectal cancer	Disease Info
Drug	Cisplatin	Drug Info

m6A Target: Glucose-induced degradation protein 8 homolog (GID8)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05270		Crosstalk Info
Epigenetic Regulator	hsa-miR-136-5p
Regulated Target	YTH domain-containing family protein 1 (YTHDF1)
Crosstalk relationship	ncRNA → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Pyruvate kinase PKM (PKM2/PKM)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05322		Crosstalk Info
Epigenetic Regulator	hsa-miR-16-5p
Regulated Target	YTH domain-containing family protein 1 (YTHDF1)
Crosstalk relationship	ncRNA → m6A
Disease	Breast cancer	Disease Info

m6A Target: Oxidized low-density lipoprotein receptor 1 (OLR1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05359		Crosstalk Info
Epigenetic Regulator	Circ_TTLL13
Regulated Target	YTH domain-containing family protein 1 (YTHDF1)
Crosstalk relationship	ncRNA → m6A
Disease	Brain cancer	Disease Info
Drug	Temozolomide	Drug Info

m6A Target: Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05405		Crosstalk Info
Epigenetic Regulator	Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)
Regulated Target	Transcriptional coactivator YAP1 (YAP1)
Crosstalk relationship	m6A → ncRNA
Disease	Non-small cell lung cancer	Disease Info
Drug	Cisplatin	Drug Info

m6A Target: hsa-miR-1914-3p

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05408		Crosstalk Info
Epigenetic Regulator	hsa-miR-1914-3p
Regulated Target	Transcriptional coactivator YAP1 (YAP1)
Crosstalk relationship	m6A → ncRNA
Disease	Non-small cell lung cancer	Disease Info
Drug	Cisplatin	Drug Info

m6A Target: Testis associated oncogenic lncRNA (THORLNC)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05443		Crosstalk Info
Epigenetic Regulator	Testis associated oncogenic lncRNA (THORLNC)
Crosstalk relationship	m6A → ncRNA

m6A Target: Long intergenic non-protein coding RNA 901 (LINC00901)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05672		Crosstalk Info
Epigenetic Regulator	Long intergenic non-protein coding RNA 901 (LINC00901)
Regulated Target	Insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2)
Crosstalk relationship	m6A → ncRNA
Disease	Pancreatic cancer	Disease Info

m6A Target: pre-miR-665

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05829		Crosstalk Info
Epigenetic Regulator	hsa-miR-665
Regulated Target	Homeobox protein DLX-3 (DLX3)
Crosstalk relationship	m6A → ncRNA
Disease	Structural developmental anomalies of teeth and periodontal tissues	Disease Info

Xenobiotics Compound(s) Regulating the m6A Methylation Regulator

Compound Name	MO-I-500	Investigative
Description	Perturbed m6A signaling can be contributing toAlzheimer's disease pathogenesis, likely by compromising astrocyte bioenergetics. MO-I-500, a novel pharmacological inhibitor of FTO, can strongly reduce the adverse effects of STZ. STZ-treated astrocytes expressed significantly higher levels of m6A demethylase FTO and m6A reader YTHDF1.	[116]
Compound Name	AdoHcy	Investigative
Synonyms	S-Adenosyl-L-homocysteine; S-adenosylhomocysteine; S-adenosyl-L-homocysteine; 979-92-0; AdoHcy; S-(5'-adenosyl)-L-homocysteine; adenosylhomocysteine; Formycinylhomocysteine; Adenosyl-L-homocysteine; S-(5'-deoxyadenosin-5'-yl)-L-homocysteine; 2-S-adenosyl-L-homocysteine; 5'-Deoxy-S-adenosyl-L-homocysteine; S-adenosyl-homocysteine; S-Adenosyl Homocysteine; L-S-Adenosylhomocysteine; L-Homocysteine, S-(5'-deoxyadenosin-5'-yl)-; adenosylhomo-cys; adenosyl-homo-cys; UNII-8K31Q2S66S; (S)-5'-(S)-(3-Amino-3-carboxypropyl)-5'-thioadenosine; BRN 5166233; SAH; S-Adenosylhomocysteine; S-Adenosyl-L-Homocysteine Click to Show/Hide
External link	CID: 439155 TTD: D09CLP DrugBank: DB01752
Description	Mettl3 inhibitor, S-adenosylhomocysteine promoted the apoptosis and autophagy of chondrocytes with inflammation in vitro and aggravated the degeneration of chondrocytes and subchondral bone in monosodium iodoacetate (MIA) inducedtemporomandibular joint osteoarthritis mice in vivo. Bcl2 protein interacted with Beclin1 protein in chondrocytes induced by TNF-alpha stimulation. Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through m6A/Ythdf1/Bcl2 signal axis which provides promising therapeutic strategy fortemporomandibular joint osteoarthritis.	[25]
Compound Name	Olean-28,13Beta-lactam(B28)	Investigative
Description	B28 disrupts YTDFH1-GLS1 axis to induce ROS-dependent cell bioenergetics crisis and cell death which finally suppress PAAD cell growth, indicating that this synthesized olean-28,13Beta-lactam maybe a potent agent for PAAD intervention.	[119]

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Correspondence

Prof. Feng ZHU

Prof. Shuiping Liu

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