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.

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.

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.

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.

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.

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				[37]
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.

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.

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				[38]
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				[39]
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.

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				[40]
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.

Mammalian target of rapamycin complex 2 (mTORC2)

Target Gene

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				[41]
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.

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		[42]
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		[43]
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.

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.

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				[44]
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.

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		[45]
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.

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

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				[46]
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.

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				[47]
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.

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				[48]
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				[48]
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				[49]
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				[50]
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.

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				[53]
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.

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.

Mammalian target of rapamycin complex 2 (mTORC2)

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				[41]
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.

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.

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.

Unspecific Target Gene

Fluorouracil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[48]
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				[48]
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				[49]
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

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.	[53]
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.	[54]

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m6A Regulator Information

Cite M6AREG

Correspondence

Prof. Feng ZHU

Prof. Shuiping Liu

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