m6A Regulator Information

General Information of the m6A Regulator (ID: REG00008)

Regulator Name	YTH domain-containing family protein 2 (YTHDF2)
Synonyms	DF2; CLL-associated antigen KW-14; High-glucose-regulated protein 8; Renal carcinoma antigen NY-REN-2; HGRG8 Click to Show/Hide
Gene Name	YTHDF2
Sequence	MSASSLLEQRPKGQGNKVQNGSVHQKDGLNDDDFEPYLSPQARPNNAYTAMSDSYLPSYY SPSIGFSYSLGEAAWSTGGDTAMPYLTSYGQLSNGEPHFLPDAMFGQPGALGSTPFLGQH GFNFFPSGIDFSAWGNNSSQGQSTQSSGYSSNYAYAPSSLGGAMIDGQSAFANETLNKAP GMNTIDQGMAALKLGSTEVASNVPKVVGSAVGSGSITSNIVASNSLPPATIAPPKPASWA DIASKPAKQQPKLKTKNGIAGSSLPPPPIKHNMDIGTWDNKGPVAKAPSQALVQNIGQPT QGSPQPVGQQANNSPPVAQASVGQQTQPLPPPPPQPAQLSVQQQAAQPTRWVAPRNRGSG FGHNGVDGNGVGQSQAGSGSTPSEPHPVLEKLRSINNYNPKDFDWNLKHGRVFIIKSYSE DDIHRSIKYNIWCSTEHGNKRLDAAYRSMNGKGPVYLLFSVNGSGHFCGVAEMKSAVDYN TCAGVWSQDKWKGRFDVRWIFVKDVPNSQLRHIRLENNENKPVTNSRDTQEVPLEKAKQV LKIIASYKHTTSIFDDFSHYEKRQEEEESVKKERQGRGK Click to Show/Hide
Family	YTHDF family; YTHDF2 subfamily
Function	Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, 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 and ribonuclease P/MRP complexes, depending on the context. The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation. M6A-containing mRNAs containing a binding site for RIDA/HRSP12 (5'-GGUUC-3') are preferentially degraded by endoribonucleolytic cleavage: cooperative binding of RIDA/HRSP12 and YTHDF2 to transcripts leads to recruitment of the ribonuclease P/MRP complex. Other m6A-containing mRNAs undergo deadenylation via direct interaction between YTHDF2 and CNOT1, leading to recruitment of the CCR4-NOT and subsequent deadenylation of m6A-containing mRNAs. Required maternally to regulate oocyte maturation: probably acts by binding to m6A-containing mRNAs, thereby regulating maternal transcript dosage during oocyte maturation, which is essential for the competence of oocytes to sustain early zygotic development (By similarity). Also required during spermatogenesis: regulates spermagonial adhesion by promoting degradation of m6A-containing transcripts coding for matrix metallopeptidases (By similarity). Also involved in hematopoietic stem cells specification by binding to m6A-containing mRNAs, leading to promote their degradation. Also acts as a regulator of neural development by promoting m6A-dependent degradation of neural development-related mRNA targets (By similarity). Inhibits neural specification of induced pluripotent stem cells by binding to methylated neural-specific mRNAs and promoting their degradation, thereby restraining neural differentiation. Regulates circadian regulation of hepatic lipid metabolism: acts by promoting m6A-dependent degradation of PPARA transcripts. Regulates the innate immune response to infection by inhibiting the type I interferon response: acts by binding to m6A-containing IFNB transcripts and promoting their degradation. May also act as a promoter of cap-independent mRNA translation following heat shock stress: upon stress, relocalizes to the nucleus and specifically binds mRNAs with some m6A methylation mark at their 5'-UTR, protecting demethylation of mRNAs by FTO, thereby promoting cap-independent mRNA translation. Regulates mitotic entry by promoting the phase-specific m6A-dependent degradation of WEE1 transcripts . 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. May also recognize and bind RNAs modified by C5-methylcytosine (m5C) and act as a regulator of rRNA processing; (Microbial infection) Promotes viral gene expression and virion production of kaposis sarcoma-associated herpesvirus (KSHV) at some stage of the KSHV life cycle (in iSLK.219 and iSLK.BAC16 cells). Acts by binding to N6-methyladenosine (m6A)-containing viral RNAs. Click to Show/Hide
Gene ID	51441
Uniprot ID	YTHD2_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)

YTHDF2 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

Arrestin domain-containing protein 4 (ARRDC4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Human umbilical cord blood CD34+ cells	Homo sapiens
Treatment: YTHDF2 knockdown UCB CD34+ cells Control: Wild type UCB CD34+ cells		GSE107956
Regulation		logFC: -8.12E-01 p-value: 3.74E-05
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.87E+00	GSE49339

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				[1]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation
Pathway Response	mRNA surveillance pathway			hsa03015), RNA degradation
Cell Process	RNA stability
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	NCM460	Normal	Homo sapiens	CVCL_0460
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HCT 15	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vivo Model	Equal amount of HCT116 cells (2 × 10⁶) stably expression of relevant plasmids was injected into the right flank of mice, tumor bulks was monitored once a week after injection and volumes were counted as 0.5 × a2 × b (a and b respectively indicated short and long diameter of tumor).
Response Summary	Knockdown of METTL14 significantly enhanced Arrestin domain-containing protein 4 (ARRDC4) mRNA stability relying on the "reader" protein YTHDF2 dependent manner in colorectal cancer.

Bcl-2-modifying factor (BMF)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Human umbilical cord blood CD34+ cells	Homo sapiens
Treatment: YTHDF2 knockdown UCB CD34+ cells Control: Wild type UCB CD34+ cells		GSE107956
Regulation		logFC: 1.29E+00 p-value: 2.46E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.27E+00	GSE49339

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				[2]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Target Regulation	Down regulation
Cell Process	RNA stability
Cell Process	Cell apoptosis
In-vitro Model	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	OVCAR-8	High grade ovarian serous adenocarcinoma	Homo sapiens	CVCL_1629
	OVCA429	Ovarian cystadenocarcinoma	Homo sapiens	CVCL_3936
	OVCA420	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_3935
In-vivo Model	5 × 10⁶ cells were suspended in 100 uL PBS and then were inoculated subcutaneously.
Response Summary	FBW7 suppresses tumor growth and progression via antagonizing YTHDF2-mediated Bcl-2-modifying factor (BMF) mRNA decay in ovarian cancer.

C-X-C chemokine receptor type 4 (CXCR4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Testis	Mus musculus
Treatment: YTHDF2 knockout mice testis Control: Mice testis		GSE147574
Regulation		logFC: 7.39E-01 p-value: 4.60E-02
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.20E+00	GSE49339

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				[3]
Responsed Disease	Melanoma [ICD-11: 2C30]
Responsed Drug	PMID31239444-anti-PD1 antibody		Investigative	Drug Info
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	mRNA decay
In-vitro Model	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
	CHL-1	Melanoma	Homo sapiens	CVCL_1122
	624-mel	Melanoma	Homo sapiens	CVCL_8054
	NHEM (Normal Human Epidermal Melanocytes)
	SK-MEL-30	Cutaneous melanoma	Homo sapiens	CVCL_0039
	WM115	Melanoma	Homo sapiens	CVCL_0040
	WM35	Melanoma	Homo sapiens	CVCL_0580
	WM3670	Melanoma	Homo sapiens	CVCL_6799
	WM793	Melanoma	Homo sapiens	CVCL_8787
In-vivo Model	When the tumors reached a volume of 80-100 mm³, mice were treated with anti-PD-1 or isotype control antibody (200 ug/mouse) by i.p. injection, every other day for three times. For IFNγ blockade treatment, C57BL/6 mice were treated with anti-IFNγ antibody or isotype control IgG (250 ug/mouse) every other day after tumor cell inoculation.
Response Summary	These findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade reduces the resistance to immunotherapy in melanoma. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), C-X-C chemokine receptor type 4 (CXCR4), and SOX10, leading to increased RNA decay through the m6A reader YTHDF2.

Ephrin type-B receptor 3 (EPHB3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Mouse-cerebellum granule cell	Mus musculus
Treatment: YTHDF2 knockdown mouse-cerebellum granule cell Control: Wild type mouse-cerebellum granule cell		GSE153688
Regulation		logFC: -6.25E-01 p-value: 1.90E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.21E+00	GSE49339

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				[4]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Responsed Drug	Temozolomide		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	RNA stability
In-vitro Model	T98G	Glioblastoma	Homo sapiens	CVCL_0556
In-vitro Model	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
In-vivo Model	5 × 10⁶ infected T98G cells (LV-NC or LV-YTHDF2) were injected into the flanks of mice through subcutaneous.
Response Summary	YTHDF2 enhanced TMZ resistance in GBM by activation of the PI3K/Akt and NF-Kappa-B signalling pathways via inhibition of Ephrin type-B receptor 3 (EPHB3) and TNFAIP3.

Homeobox protein Nkx-3.1 (NKX3-1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	GSC11 cell line	Homo sapiens
Treatment: siYTHDF2 GSC11 cells Control: siControl GSC11 cells		GSE142825
Regulation		logFC: 9.36E-01 p-value: 4.17E-02
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.20E+00	GSE49339

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[5]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Down regulation
Pathway Response	Oxidative phosphorylation			hsa00190
In-vitro Model	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	RWPE-1	Normal	Homo sapiens	CVCL_3791
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
In-vivo Model	Approximately 2 × 10⁶ PCa cells (PC-3 shNC, shYTHDF2, shMETTL3 cell lines) per mouse suspended in 100 uL PBS were injected in the flank of male BALB/c nude mice (4 weeks old). During the 40-day observation, the tumor size (V = (width2×length ×0.52)) was measured with vernier caliper. Approximately 1.5 × 10⁶ PCa cells suspended in 100 uL of PBS (PC-3 shNC, shYTHDF2, and shMETTL3 cell lines) per mouse were injected into the tail vein of male BALB/c nude mice (4 weeks old). The IVIS Spectrum animal imaging system (PerkinElmer) was used to evaluate the tumor growth (40 days) and whole metastasis conditions (4 weeks and 6 weeks) with 100 uL XenoLight D-luciferin Potassium Salt (15 mg/ml, Perkin Elmer) per mouse. Mice were anesthetized and then sacrificed for tumors and metastases which were sent for further organ-localized imaging as above, IHC staining and hematoxylin-eosin (H&E) staining.
Response Summary	Knock-down of YTHDF2 or METTL3 significantly induced the expression of LHPP and Homeobox protein Nkx-3.1 (NKX3-1) at both mRNA and protein level with inhibited phosphorylated AKT. YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer.

Krueppel-like factor 4 (KLF4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	GSC11 cell line	Homo sapiens
Treatment: siYTHDF2 GSC11 cells Control: siControl GSC11 cells		GSE142825
Regulation		logFC: 6.24E-01 p-value: 8.92E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.55E+00	GSE49339

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				[6]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Down regulation
Pathway Response	TNF signaling pathway			hsa04668
Cell Process	Cell migration
	Cell invasion
	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Response Summary	MiR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor Krueppel-like factor 4 (KLF4). miR-1915-3p function as a tumor suppressor by targeting SET and has an anti-metastatic therapeutic potential for lung cancer treatment.

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[7]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Down regulation
Cell Process	Cancer proliferation
	Cancer metastasis
In-vitro Model	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
In-vivo Model	For the subcutaneous implantation model, UM-UC-3 cells (2 × 10⁶ cells per mouse) stably METTL3 knocked down (shMETTL3-1, shMETTL3-2) were injected into the flanks of mice.
Response Summary	METTL3/YTHDF2/SETD7/Krueppel-like factor 4 (KLF4) m6 A axis provide the insight into the underlying mechanism of carcinogenesis and highlight potential therapeutic targets for bladder cancer.

MOB kinase activator 3B (MOB3B)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	GSC11 cell line	Homo sapiens
Treatment: siYTHDF2 GSC11 cells Control: siControl GSC11 cells		GSE142825
Regulation		logFC: -6.21E-01 p-value: 1.40E-08
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.42E+00	GSE49339

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[8]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Down regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	LNCaP C4-2	Prostate carcinoma	Homo sapiens	CVCL_4782
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
In-vivo Model	Under anesthesia with ether, the nude mice were disinfected and subcutaneously inoculated with cells transfected with oe-NC, oe-KDM5A + oe-NC and oe-KDM5A + oe-MOB3B at a density of 1 × 10⁶ cells/mouse (200 uL) at the back of the right hind leg.
Response Summary	Activation of the KDM5A/miRNA-495/YTHDF2/m6A-MOB3B axis facilitates prostate cancer progression. YTHDF2 could inhibit MOB kinase activator 3B (MOB3B) expression by recognizing m6A modification of MOB3B mRNA and inducing mRNA degradation.

Mothers against decapentaplegic homolog 3 (SMAD3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: shYthdf2 embryonic stem cells Control: shLuc embryonic stem cells		GSE156437
Regulation		logFC: 5.96E-01 p-value: 6.99E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.21E+00	GSE49339

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	Lung cancer [ICD-11: 2C25]
Target Regulation	Down regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Response Summary	YTHDF2 inhibits the migration and invasion of lung adenocarcinoma cells by regulating the FAM83D-TGFbeta1-Mothers against decapentaplegic homolog 3 (SMAD3) pathway, which will play an important role in lung cancer metastasis.

Mothers against decapentaplegic homolog 7 (SMAD7)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Human umbilical cord blood CD34+ cells	Homo sapiens
Treatment: YTHDF2 knockdown UCB CD34+ cells Control: Wild type UCB CD34+ cells		GSE107956
Regulation		logFC: -6.53E-01 p-value: 1.90E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.67E+00	GSE49339

Inflammatory response [ICD-11: MG46]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[10]
Responsed Disease	Inflammatory response [ICD-11: MG46]
Target Regulation	Down regulation
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	RNA stability
In-vitro Model	MC3T3-E1	Normal	Mus musculus	CVCL_0409
Response Summary	METTL3 knockdown inhibits osteoblast differentiation and Smad-dependent signaling by stabilizing Mothers against decapentaplegic homolog 7 (SMAD7) and Smurf1 mRNA transcripts via YTHDF2 involvement and activates the inflammatory response by regulating MAPK signaling in LPS-induced inflammation.

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				[85]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulation	Down regulation
In-vitro Model	MRC-9	Normal	Homo sapiens	CVCL_2629
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1703	Lung squamous cell carcinoma	Homo sapiens	CVCL_1490
	H1795 (Lung cancer H1795 cell lines were purchased from ATCC, USA)
	NCI-H1792	Lung adenocarcinoma	Homo sapiens	CVCL_1495
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428

Myc proto-oncogene protein (MYC)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	GSC11 cell line	Homo sapiens
Treatment: siYTHDF2 GSC11 cells Control: siControl GSC11 cells		GSE142825
Regulation		logFC: 8.94E-01 p-value: 8.57E-07
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.40E+00	GSE49339

Brain cancer [ICD-11: 2A00]

In total 2 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[11]
Responsed Disease	Glioma [ICD-11: 2A00.0]
Responsed Drug	Linsitinib	Phase 3	Drug Info
Target Regulation	Up regulation
Pathway Response	RNA degradation		hsa03018
Cell Process	RNA stability
In-vitro Model	()
	HNP1 (A human neural progenitor cell)
	NHA (Normal human astrocytes)
	NSC11 (Pluripotent derived neural progenitor cell)
In-vivo Model	For in vivo drug treatment studies, intracranial xenografts were generated by implanting 5000 patient-derived GSCs (387 and 4121) into the right cerebral cortex of NSG mice as described above.
Response Summary	The m6A reader YTHDF2 stabilized Myc proto-oncogene protein (MYC) mRNA specifically in cancer stem cells. Given the challenge of targeting MYC, YTHDF2 presents a therapeutic target to perturb MYC signaling in glioblastoma. The IGF1/IGF1R inhibitor linsitinib preferentially targeted YTHDF2-expressing cells, inhibiting GSC viability without affecting NSCs and impairing in vivo glioblastoma growth. YTHDF2 links RNA epitranscriptomic modifications and GSC growth, laying the foundation for the YTHDF2-MYC-IGFBP3 axis as a specific and novel therapeutic target in glioblastoma.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene			[86]
Responsed Disease	Brain cancer [ICD-11: 2A00]
Target Regulation	Up regulation

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[12]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Tamoxifen		Approved	Drug Info
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	Epithelial-to-mesenchymal transition
Cell Process	Cell apoptosis
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MBA-MD-231 (Human breast cancer cell)
	MYC-ER HMEC (Human mammary epithelial cells expressing a MYC estrogen receptor fusion)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
In-vivo Model	To induce recombination at 8 weeks of age both CAG-CreERT;Ythdf2^fl/fl and Ythdf2^fl/fl littermates were injected with 75mg/kg body weight tamoxifen dissolved in corn oil daily for 5 days.
Response Summary	LCAT3 upregulation is attributable to m6A modification mediated by METTL3, leading to LCAT3 stabilization. Treated cells with tamoxifen to induce MYC activity. Highlights the therapeutic potential of RBPs by uncovering a critical role for YTHDF2 in counteracting the global increase of mRNA synthesis in Myc proto-oncogene protein (MYC)-driven breast cancers.

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		[75]
Responsed Disease	Liver hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Down regulation
In-vivo Model	Male BALB/c nude mice (aged 4-6 weeks; n = 5/group) were obtained from Vital River Laboratory Animal Technology (Beijing, China). MHCC97H or Huh7 cells (2 × 10⁶ cells/mouse) stably transfected with lentivirus containing different plasmids in 100 μL DMEM were subcutaneously or orthotopically implanted into the nude mice.

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		[85]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulation	Down regulation

Peroxisome proliferator-activated receptor alpha (PPARalpha/PPARA)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	GSC11 cell line	Homo sapiens
Treatment: siYTHDF2 GSC11 cells Control: siControl GSC11 cells		GSE142825
Regulation		logFC: 7.24E-01 p-value: 8.81E-04
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.45E+00	GSE49339

Metabolic disorders [ICD-11: 5D2Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[13]
Responsed Disease	Metabolic disorders [ICD-11: 5D2Z]
Target Regulation	Down regulation
Pathway Response	PPAR signaling pathway			hsa03320
	Adipocytokine signaling pathway			hsa04920
Cell Process	Llipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hepa 1-6	Hepatocellular carcinoma of the mouse	Mus musculus	CVCL_0327
In-vivo Model	Liver-specific Bmal1^f/f-AlbCre-knockout mice were purchased from Jackson Laboratory. C57BI/6J or Bmal1^f/f-AlbCre-knockout male mice were maintained under a 12 hr light/12 hr dark (LD) cycle (ZT0 = 6 AM) and fed ad libitum with normal rodent chow (2018 Global 18% Protein diet, Envigo) and water. At 10-14 weeks of age, 10 male mice per group were sacrificed via CO2 asphyxiation at Zeitgeber Time (ZT) 0,2,6,10,12,14,18,22. In order to induce high levels of ROS in the liver, WT male mice were fasted 12 h and followed by intraperitoneal injection with 300 mg/kg APAP dissolved in PBS and re-fed.
Response Summary	PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Hepatic deletion of Bmal1 increases m6A mRNA methylation, particularly of Peroxisome proliferator-activated receptor alpha (PPARalpha/PPARA). Inhibition of m6A methylation via knockdown of m6A methyltransferase METTL3 decreases PPaR-Alpha m6A abundance and increases PPaRalpha mRNA lifetime and expression, reducing lipid accumulation in cells in vitro. YTHDF2 binds to PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Transcriptional regulation of circadian rhythms is essential for lipid metabolic homeostasis, disruptions of which can lead to metabolic diseases.

Platelet-derived growth factor C (PDGFC)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	GSC11 cell line	Homo sapiens
Treatment: siYTHDF2 GSC11 cells Control: siControl GSC11 cells		GSE142825
Regulation		logFC: 8.71E-01 p-value: 1.24E-12
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.41E+00	GSE49339

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				[14]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	SW1990	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	HPDE	Normal	Homo sapiens	CVCL_4376
	CFPAC-1	Cystic fibrosis	Homo sapiens	CVCL_1119
	Capan-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0237
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	The right flanks of mice were injected subcutaneously with 2 × 10⁶ MiaPaCa-2 cells stably expressing shFTO and a scrambled shRNA in 100 uL PBS. Tumors were measured using an external caliper once per week, and tumor volume was calculated with the formula: (length × width2)/2.
Response Summary	FTO downregulation leads to increased m6A modifications in the 3' UTR of Platelet-derived growth factor C (PDGFC) and then modulates the degradation of its transcriptional level in an m6A-YTHDF2-dependent manner, highlighting a potential therapeutic target for PDAC treatment and prognostic prediction.

Protein FAM83D (FAM83D)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Human umbilical cord blood CD34+ cells	Homo sapiens
Treatment: YTHDF2 knockdown UCB CD34+ cells Control: Wild type UCB CD34+ cells		GSE107956
Regulation		logFC: 1.01E+00 p-value: 7.31E-07
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.69E+00	GSE49339

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	Lung cancer [ICD-11: 2C25]
Target Regulation	Down regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Response Summary	YTHDF2 inhibits the migration and invasion of lung adenocarcinoma cells by regulating the Protein FAM83D (FAM83D)-TGFbeta1-pSMAD2/3 pathway, which will play an important role in lung cancer metastasis.

Suppressor of cytokine signaling 2 (SOCS2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Human umbilical cord blood CD34+ cells	Homo sapiens
Treatment: YTHDF2 knockdown UCB CD34+ cells Control: Wild type UCB CD34+ cells		GSE107956
Regulation		logFC: 9.71E-01 p-value: 1.71E-04
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.81E+00	GSE49339

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				[15]
Responsed Disease	Liver cancer [ICD-11: 2C12]
Target Regulation	Down regulation
Cell Process	Cells proliferation
	Cells migration
	Cells invasion
	RNA degradation (hsa03018)
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	MHCC97-L	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4973
In-vivo Model	For the subcutaneous implantation model, 2 × 10⁶ METTL3 stable knockdown Huh-7 cells or METTL3 overexpression MHCC97L cells were injected subcutaneously into BABL/cAnN-nude mice. For orthotopic implantation, wild-type and METTL3 knockout Huh-7 cells were luciferase labelled, and 2 × 10⁶ cells were then injected orthotopically into the left liver lobe of nude mice.
Response Summary	METTL3 is frequently up-regulated in human HCC and contributes to HCC progression. METTL3 represses Suppressor of cytokine signaling 2 (SOCS2) expression in HCC through an m6A-YTHDF2-dependent mechanism.

Suppressor of cytokine signaling 3 (SOCS3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: shYthdf2 embryonic stem cells Control: shLuc embryonic stem cells		GSE156437
Regulation		logFC: -1.05E+00 p-value: 3.86E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.46E+00	GSE49339

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[16]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Down regulation
Pathway Response	JAK-STAT signaling pathway			hsa04630
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	OS3 [Human osteosarcoma]	Osteosarcoma	Homo sapiens	CVCL_F866
	OS2 [Human osteosarcoma]	Osteosarcoma	Homo sapiens	CVCL_F865
	OS1 [Human osteosarcoma]	Osteosarcoma	Homo sapiens	CVCL_F864
	KHOS/NP	Osteosarcoma	Homo sapiens	CVCL_2546
Response Summary	ALKBH5 inactivated STAT3 pathway by increasing Suppressor of cytokine signaling 3 (SOCS3) expression via an m6A-YTHDF2-dependent manner.Reducing m6A mRNA levels in human osteosarcoma cells through ALKBH5 up-regulation lead to cell proliferation inhibition, cell apoptosis and cycle arrest.

Human skin lesions [ICD-11: ME60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[110]
Responsed Disease	Human skin lesions [ICD-11: ME60]
Responsed Drug	Arsenite		Phase 2	Drug Info
Target Regulation	Down regulation
Pathway Response	JAK-STAT signaling pathway			hsa04630
In-vitro Model	HaCaT	Normal	Homo sapiens	CVCL_0038

Thrombospondin-1 (THBS1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Human umbilical cord blood CD34+ cells	Homo sapiens
Treatment: YTHDF2 knockdown UCB CD34+ cells Control: Wild type UCB CD34+ cells		GSE107956
Regulation		logFC: -9.06E-01 p-value: 2.97E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.48E+00	GSE49339

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[17]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Down regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	Cell proliferation
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
In-vitro Model	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
In-vivo Model	Stably transfected shMETTL14 and shNC DU145 cells (5×10⁶ cells) suspended in a mixture of 100uL PBS were subcutaneously injected into the right flank of male nude BALB/C mice (6-8 weeks old) to induce tumor formation.
Response Summary	In prostate cancer, METTL14 downregulated Thrombospondin-1 (THBS1) expression in an m6A-dependent manner, which resulted in the recruitment of YTHDF2 to recognize and degrade Thrombospondin 1 (THBS1) mRNA.

Transcription factor HIVEP2 (HIVEP2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	GSC11 cell line	Homo sapiens
Treatment: siYTHDF2 GSC11 cells Control: siControl GSC11 cells		GSE142825
Regulation		logFC: 1.16E+00 p-value: 1.15E-15
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.70E+00	GSE49339

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				[18]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Target Regulation	Down regulation
Pathway Response	mRNA surveillance pathway			hsa03015), RNA degradation
Cell Process	RNA stability
In-vitro Model	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
	U-251MG	Astrocytoma	Homo sapiens	CVCL_0021
	T98G	Glioblastoma	Homo sapiens	CVCL_0556
	SW1783	Anaplastic astrocytoma	Homo sapiens	CVCL_1722
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	Hs 683	Oligodendroglioma	Homo sapiens	CVCL_0844
	GSC7-2 (GSC7-2 were obtained from fresh surgical specimens of human primary and recurrent glioma)
	GSC6-27 (GSC6-27 were obtained from fresh surgical specimens of human primary and recurrent glioma)
	GSC23	Glioblastoma	Homo sapiens	CVCL_DR59
	GSC20 (GSC20 were obtained from fresh surgical specimens of human primary and recurrent glioma)
	GSC17	Glioblastoma	Homo sapiens	CVCL_DR57
	GSC11	Glioblastoma	Homo sapiens	CVCL_DR55
In-vivo Model	For the studies of investigating mice survival, mice were intracranially injected with 10,000 GSC11, 10,000 GSC7-2, or 500,000 LN229 cells.
Response Summary	YTHDF2 facilitates m6A-dependent mRNA decay of LXRA and Transcription factor HIVEP2 (HIVEP2), which impacts the glioma patient survival. YTHDF2 promotes tumorigenesis of GBM cells, largely through the downregulation of LXRA and HIVEP2.

Transcription factor SOX-4 (SOX4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	GSC11 cell line	Homo sapiens
Treatment: siYTHDF2 GSC11 cells Control: siControl GSC11 cells		GSE142825
Regulation		logFC: 8.56E-01 p-value: 4.96E-15
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.82E+00	GSE49339

Endometrial cancer [ICD-11: 2C76]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[19]
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	HEC-1-B	Endometrial adenocarcinoma	Homo sapiens	CVCL_0294
Response Summary	YTHDF2-mediated LncRNA FENDRR degradation promotes cell proliferation by elevating Transcription factor SOX-4 (SOX4) expression in endometrioid endometrial carcinoma.

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[113]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
In-vitro Model	NCM460	Normal	Homo sapiens	CVCL_0460
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
In-vivo Model	All animal experiments were approved by the animal care Committee of Nanjing First Hospital, Nanjing Medial University (acceptance No. SYXK 20160006). 2 × 10⁶ transfected HCT116 cells in 0.2 ml PBS were injected into the tail vein of nude mice which were randomly divided into nine groups (eight mice per group). After 3 months of injection, mice were sacrificed, and their lungs were removed and stained by Hematoxylin and Eosin (HE) Staining.

Transcriptional coactivator YAP1 (YAP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	GSC11 cell line	Homo sapiens
Treatment: siYTHDF2 GSC11 cells Control: siControl GSC11 cells		GSE142825
Regulation		logFC: 7.52E-01 p-value: 2.51E-07
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.34E+00	GSE49339

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				[20]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
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.

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				[21]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Down regulation
Pathway Response	Hippo signaling pathway			hsa04390
Cell Process	Cells proliferation
	Cells migration
	Cells invasion
	Epithelial-mesenchymal transition
In-vitro Model	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	PaTu 8988s	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1846
	SW1990	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
Response Summary	YTHDF2 knockdown significantly increases the total YAP expression, but inhibits TGF-beta/Smad signaling, indicating that YTHDF2 regulates EMT probably via Transcriptional coactivator YAP1 (YAP1) signaling. YTHDF2 is a new predictive biomarker of development of pancreatic cancer.

Triple-negative breast cancer [ICD-11: 2C6Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[114]
Responsed Disease	Triple-negative breast cancer [ICD-11: 2C6Z]
Target Regulation	Down regulation

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

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	B18-hi B cell line	Mus musculus
Treatment: YTHDF2 knockout B18-hi B cells Control: Wild type B18-hi B cells		GSE189819
Regulation		logFC: -7.97E-01 p-value: 5.55E-03
More Results	Click to View More RNA-seq Results

Metabolic disorders [ICD-11: 5D2Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[13]
Responsed Disease	Metabolic disorders [ICD-11: 5D2Z]
Target Regulation	Down regulation
Pathway Response	PPAR signaling pathway			hsa03320
	Adipocytokine signaling pathway			hsa04920
Cell Process	Llipid metabolism
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Hepa 1-6	Hepatocellular carcinoma of the mouse	Mus musculus	CVCL_0327
In-vivo Model	Liver-specific Bmal1^f/f-AlbCre-knockout mice were purchased from Jackson Laboratory. C57BI/6J or Bmal1^f/f-AlbCre-knockout male mice were maintained under a 12 hr light/12 hr dark (LD) cycle (ZT0 = 6 AM) and fed ad libitum with normal rodent chow (2018 Global 18% Protein diet, Envigo) and water. At 10-14 weeks of age, 10 male mice per group were sacrificed via CO2 asphyxiation at Zeitgeber Time (ZT) 0,2,6,10,12,14,18,22. In order to induce high levels of ROS in the liver, WT male mice were fasted 12 h and followed by intraperitoneal injection with 300 mg/kg APAP dissolved in PBS and re-fed.
Response Summary	PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Hepatic deletion of Brain and muscle ARNT-like 1 (Bmal1/ARNTL) increases m6A mRNA methylation, particularly of PPaRalpha. Inhibition of m6A methylation via knockdown of m6A methyltransferase METTL3 decreases PPaR-Alpha m6A abundance and increases PPaRalpha mRNA lifetime and expression, reducing lipid accumulation in cells in vitro. YTHDF2 binds to PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Transcriptional regulation of circadian rhythms is essential for lipid metabolic homeostasis, disruptions of which can lead to metabolic diseases.

Death-associated protein kinase 2 (DAPK2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Human umbilical cord blood CD34+ cells	Homo sapiens
Treatment: YTHDF2 knockdown UCB CD34+ cells Control: Wild type UCB CD34+ cells		GSE107956
Regulation		logFC: 1.13E+00 p-value: 1.77E-04
More Results	Click to View More RNA-seq Results

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[22]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Down regulation
In-vitro Model	NCI-H838	Lung adenocarcinoma	Homo sapiens	CVCL_1594
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	The nude mice were maintained under pathogen-free conditions and kept under timed lighting conditions mandated by the committee with food and water provided ad libitum. For xenograft experiments, nude mice were injected subcutaneously with 5 × 10⁶ cells resuspended in 0.1 mL PBS. When a tumor was palpable, it was measured every 3 days.
Response Summary	Cigarette smoking induced aberrant N6-methyladenosine modification of Death-associated protein kinase 2 (DAPK2), which resulted in decreased DAPK2 mRNA stability and expression of its mRNA and protein. This modification was mediated by the m6A "writer" METTL3 and the m6A "reader" YTHDF2. BAY 11-7085, a NF-Kappa-B signaling selective inhibitor, was shown to efficiently suppressed downregulation of DAPK2-induced oncogenic phenotypes of NSCLC cells.

E3 ubiquitin-protein ligase TRIM7 (TRIM7)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Mouse-cerebellum granule cell	Mus musculus
Treatment: YTHDF2 knockdown mouse-cerebellum granule cell Control: Wild type mouse-cerebellum granule cell		GSE153688
Regulation		logFC: 1.15E+00 p-value: 8.92E-03
More Results	Click to View More RNA-seq Results

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[23]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Down regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Proteasome pathway degradation
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
In-vivo Model	MG63 cells transduced with lentivirus expressing shTRIM7 or shNC, and SAOS2 cells transduced with lentivirus expressing TRIM7, BRMS1, TRIM7 plus BRMS1 or control vector, were injected via the tail vein into the nude mice (1 × 10⁶ cells/mouse) (n = 11 per group).
Response Summary	E3 ubiquitin-protein ligase TRIM7 (TRIM7) mRNA stability was regulated by the METTL3/14-YTHDF2-mRNA in a decay-dependent manner. TRIM7 plays a key role in regulating metastasis and chemoresistance in osteosarcoma through ubiquitination of BRMS1.

Endoplasmic reticulum chaperone BiP (Grp78)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	B18-hi B cell line	Mus musculus
Treatment: YTHDF2 knockout B18-hi B cells Control: Wild type B18-hi B cells		GSE189819
Regulation		logFC: 1.16E+00 p-value: 1.91E-04
More Results	Click to View More RNA-seq Results

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

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[24]
Responsed Disease	Diseases of the musculoskeletal system [ICD-11: FC0Z]
Target Regulation	Down regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	RNA stability
In-vitro Model	MC3T3-E1	Normal	Mus musculus	CVCL_0409
Response Summary	METTL3 knockdown enhanced Endoplasmic reticulum chaperone BiP (Grp78) expression through YTHDF2-mediated RNA degradation, which elicited ER stress, thereby promoting osteoblast apoptosis and inhibiting cell proliferation and differentiation under LPS-induced inflammatory condition.

G1/S-specific cyclin-D1 (CCND1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	GSC11 cell line	Homo sapiens
Treatment: siYTHDF2 GSC11 cells Control: siControl GSC11 cells		GSE142825
Regulation		logFC: 1.13E+00 p-value: 1.41E-27
More Results	Click to View More RNA-seq Results

Obesity [ICD-11: 5B81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[25]
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Mitotic clonal
	Prolonged G1/S transition
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Response Summary	Obesity is becoming a global problem. ZFP217 knockdown-induced adipogenesis inhibition was caused by G1/S-specific cyclin-D1 (CCND1), which was mediated by METTL3 and YTHDF2 in an m6A-dependent manner.

Glia-derived nexin (SERPINE2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Human umbilical cord blood CD34+ cells	Homo sapiens
Treatment: YTHDF2 knockdown UCB CD34+ cells Control: Wild type UCB CD34+ cells		GSE107956
Regulation		logFC: 1.40E+00 p-value: 3.23E-07
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				[27]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Down regulation
Pathway Response	HIF-1 signaling pathway			hsa04066
Cell Process	Biological regulation
In-vitro Model	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
In-vitro Model	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	A number of 5 × 10⁶ SMMC7721 or MHCC97H cells re-suspended in 100 uL of PBS were subcutaneously injected into the right flank of 6-week old male NCG mice.
Response Summary	YTHDF2 processed the decay of m6A-containing interleukin 11 (IL11) and Glia-derived nexin (SERPINE2) mRNAs. YTHDF2 transcription succumbed to hypoxia-inducible factor-2-alpha (HIF-2-alpha). Administration of a HIF-2-alpha antagonist (PT2385) restored YTHDF2-programed epigenetic machinery and repressed liver cancer.

Histone-lysine N-methyltransferase SETD7 (SETD7)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Human umbilical cord blood CD34+ cells	Homo sapiens
Treatment: YTHDF2 knockdown UCB CD34+ cells Control: Wild type UCB CD34+ cells		GSE107956
Regulation		logFC: -8.31E-01 p-value: 1.26E-02
More Results	Click to View More RNA-seq Results

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[7]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Down regulation
Cell Process	Cancer proliferation
	Cancer metastasis
In-vitro Model	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
In-vivo Model	For the subcutaneous implantation model, UM-UC-3 cells (2 × 10⁶ cells per mouse) stably METTL3 knocked down (shMETTL3-1, shMETTL3-2) were injected into the flanks of mice.
Response Summary	METTL3/YTHDF2/Histone-lysine N-methyltransferase SETD7 (SETD7)/KLF4 m6 A axis provide the insight into the underlying mechanism of carcinogenesis and highlight potential therapeutic targets for bladder cancer.

Methylcytosine dioxygenase TET1 (TET1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Mouse-cerebellum granule cell	Mus musculus
Treatment: YTHDF2 knockdown mouse-cerebellum granule cell Control: Wild type mouse-cerebellum granule cell		GSE153688
Regulation		logFC: -6.29E-01 p-value: 8.41E-05
More Results	Click to View More RNA-seq Results

Chronic pain [ICD-11: MG30]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[28]
Responsed Disease	Chronic pain [ICD-11: MG30]
Target Regulation	Down regulation
Response Summary	Downregulated spinal cord METTL3 coordinating with YTHDF2 contributes to the modulation of inflammatory pain through stabilizing upregulation of Methylcytosine dioxygenase TET1 (TET1) in spinal neurons.

Myosin-7 (Myh7)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	GSC11 cell line	Homo sapiens
Treatment: siYTHDF2 GSC11 cells Control: siControl GSC11 cells		GSE142825
Regulation		logFC: -7.12E-01 p-value: 5.98E-06
More Results	Click to View More RNA-seq Results

Congestive heart failure [ICD-11: BD10]

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	Congestive heart failure [ICD-11: BD10]
Target Regulation	Up regulation
In-vitro Model	Neonatal rat ventricular cardiomyocytes (Primary myocyte cells)
In-vivo Model	Mice were anesthetized with 0.3% sodium pentobarbital (75 mg×kg^-1) intraperitoneally, and the aortic arch was tied with a 6-0 nylon suture between the brachiocephalic and left common artery with a homemade L-shaped 26G cushion needle. After ligation, the needle was quickly removed, and the skin was closed. The sham operation was identical, except that the thread was not ligated. Moreover, mice were injected with rAAV9 (4 × 10¹¹ vector genomes (vg)/mouse) carrying an empty vector, YTHDF2 or YTH-del via the tail vein.
Response Summary	Pathological cardiac hypertrophy is a major contributor of heart failure (HF), the m6A Reader YTHDF2 suppresses cardiac hypertrophy via Myosin-7 (Myh7) mRNA decoy in an m6A-dependent manner.

Nucleobindin-1 (NUCB1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	B18-hi B cell line	Mus musculus
Treatment: YTHDF2 knockout B18-hi B cells Control: Wild type B18-hi B cells		GSE189819
Regulation		logFC: 6.95E-01 p-value: 1.62E-02
More Results	Click to View More RNA-seq Results

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[30]
Responsed Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Responsed Drug	Gemcitabine		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cell proliferation
Cell Process	Cell autophagy
In-vitro Model	SW1990	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	HEK293T	Normal	Homo sapiens	CVCL_0063
	CFPAC-1	Cystic fibrosis	Homo sapiens	CVCL_1119
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
In-vivo Model	5 × 10⁶ SW1990 cells expressing NUCB1 (oeNUCB1) or control vector (oeNC) were injected subcutaneously.
Response Summary	METTL3-mediated m6A modification on Nucleobindin-1 (NUCB1) 5'UTR via the reader YTHDF2 as a mechanism for NUCB1 downregulation in PDAC. This study revealed crucial functions of NUCB1 in suppressing proliferation and enhancing the effects of gemcitabine in pancreatic cancer cells.

Oxysterols receptor LXR-alpha (LXRA)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	GSC11 cell line	Homo sapiens
Treatment: siYTHDF2 GSC11 cells Control: siControl GSC11 cells		GSE142825
Regulation		logFC: 1.19E+00 p-value: 2.27E-13
More Results	Click to View More RNA-seq Results

Brain cancer [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[18]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Target Regulation	Down regulation
Pathway Response	mRNA surveillance pathway			hsa03015), RNA degradation
Cell Process	RNA stability
In-vitro Model	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022
	U-251MG	Astrocytoma	Homo sapiens	CVCL_0021
	T98G	Glioblastoma	Homo sapiens	CVCL_0556
	SW1783	Anaplastic astrocytoma	Homo sapiens	CVCL_1722
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	Hs 683	Oligodendroglioma	Homo sapiens	CVCL_0844
	GSC7-2 (GSC7-2 were obtained from fresh surgical specimens of human primary and recurrent glioma)
	GSC6-27 (GSC6-27 were obtained from fresh surgical specimens of human primary and recurrent glioma)
	GSC23	Glioblastoma	Homo sapiens	CVCL_DR59
	GSC20 (GSC20 were obtained from fresh surgical specimens of human primary and recurrent glioma)
	GSC17	Glioblastoma	Homo sapiens	CVCL_DR57
	GSC11	Glioblastoma	Homo sapiens	CVCL_DR55
In-vivo Model	For the studies of investigating mice survival, mice were intracranially injected with 10,000 GSC11, 10,000 GSC7-2, or 500,000 LN229 cells.
Response Summary	YTHDF2 facilitates m6A-dependent mRNA decay of Oxysterols receptor LXR-alpha (LXRA) and HIVEP2, which impacts the glioma patient survival. YTHDF2 promotes tumorigenesis of GBM cells, largely through the downregulation of LXRA and HIVEP2.

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

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[97]
Responsed Disease	Diseases of the urinary system [ICD-11: GC2Z]
In-vitro Model	MCP-5 [Mouse]	N.A.	Mus musculus	CVCL_R863

Period circadian protein homolog 1 (PER1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Mouse-cerebellum granule cell	Mus musculus
Treatment: YTHDF2 knockdown mouse-cerebellum granule cell Control: Wild type mouse-cerebellum granule cell		GSE153688
Regulation		logFC: 1.44E+00 p-value: 9.54E-09
More Results	Click to View More RNA-seq Results

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[31]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Down regulation
Pathway Response	p53 signaling pathway			hsa04115
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	CFPAC-1	Cystic fibrosis	Homo sapiens	CVCL_1119
	HPDE6c7	Normal	Homo sapiens	CVCL_0P38
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	SW1990	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
Response Summary	ALKBH5 serves as a pancreatic cancer suppressor by regulating the posttranscriptional activation of Period circadian protein homolog 1 (PER1) through m6A abolishment, which highlights a demethylation-based approach for PC diagnosis and therapy. ALKBH5 loss downregulated PER1 mRNA levels in an m6A-YTHDF2-dependent manner.

Melanoma of uvea [ICD-11: 2D0Y]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[55]
Responsed Disease	Melanoma of uvea [ICD-11: 2D0Y]
In-vitro Model	OCM-1	Amelanotic melanoma	Homo sapiens	CVCL_6934
In-vitro Model	CRMM-1	Conjunctival melanoma	Homo sapiens	CVCL_M593

Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	B18-hi B cell line	Mus musculus
Treatment: YTHDF2 knockout B18-hi B cells Control: Wild type B18-hi B cells		GSE189819
Regulation		logFC: 1.54E+00 p-value: 1.87E-02
More Results	Click to View More RNA-seq Results

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[5]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Down regulation
Pathway Response	Oxidative phosphorylation			hsa00190
In-vitro Model	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	RWPE-1	Normal	Homo sapiens	CVCL_3791
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
In-vivo Model	Approximately 2 × 10⁶ PCa cells (PC-3 shNC, shYTHDF2, shMETTL3 cell lines) per mouse suspended in 100 uL PBS were injected in the flank of male BALB/c nude mice (4 weeks old). During the 40-day observation, the tumor size (V = (width2×length ×0.52)) was measured with vernier caliper. Approximately 1.5 × 10⁶ PCa cells suspended in 100 uL of PBS (PC-3 shNC, shYTHDF2, and shMETTL3 cell lines) per mouse were injected into the tail vein of male BALB/c nude mice (4 weeks old). The IVIS Spectrum animal imaging system (PerkinElmer) was used to evaluate the tumor growth (40 days) and whole metastasis conditions (4 weeks and 6 weeks) with 100 uL XenoLight D-luciferin Potassium Salt (15 mg/ml, Perkin Elmer) per mouse. Mice were anesthetized and then sacrificed for tumors and metastases which were sent for further organ-localized imaging as above, IHC staining and hematoxylin-eosin (H&E) staining.
Response Summary	Knock-down of YTHDF2 or METTL3 significantly induced the expression of Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) and NKX3-1 at both mRNA and protein level with inhibited phosphorylated AKT. YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer.

Protein SET (SET)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	GSC11 cell line	Homo sapiens
Treatment: siYTHDF2 GSC11 cells Control: siControl GSC11 cells		GSE142825
Regulation		logFC: 7.10E-01 p-value: 6.25E-10
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				[6]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Down regulation
Pathway Response	TNF signaling pathway			hsa04668
Cell Process	Cell migration
	Cell invasion
	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Response Summary	MiR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor KLF4. miR-1915-3p function as a tumor suppressor by targeting Protein SET (SET) and has an anti-metastatic therapeutic potential for lung cancer treatment.

Protein yippee-like 5 (YPEL5)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Human umbilical cord blood CD34+ cells	Homo sapiens
Treatment: YTHDF2 knockdown UCB CD34+ cells Control: Wild type UCB CD34+ cells		GSE107956
Regulation		logFC: 7.11E-01 p-value: 1.04E-04
More Results	Click to View More RNA-seq Results

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[32]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	NCM460	Normal	Homo sapiens	CVCL_0460
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
In-vivo Model	For the xenograft model, METTL3 stable overexpressed SW620 cells (1 × 10⁷) or control cells were subcutaneously injected into the right axilla of the female anesthetized BALB/C nude mice (4-6 weeks old, 18-20 g, four mice per group), respectively. The body weight and tumor volumes (length × width2 × 0.5) were measured twice a week. After 21 days, all mice were sacrificed and tumors were surgically removed for hematoxylin-eosin (H&E) staining.For the metastasis model, MTTL3 stable overexpressed SW620 cells (1 × 10⁶) or control cells were injected into the exposed spleen of the anesthetized BALB/C nude mice, respectively. After 21 days, liver metastases were carefully detected using a fluorescent stereoscope and embedded for H&E staining.
Response Summary	METTL3-catalyzed m6A modification in CRC tumorigenesis, wherein it facilitates CRC tumor growth and metastasis through suppressing Protein yippee-like 5 (YPEL5) expression in an m6A-YTHDF2-dependent manner.

Proto-oncogene c-Rel (c-Rel)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Mouse-cerebellum granule cell	Mus musculus
Treatment: YTHDF2 knockdown mouse-cerebellum granule cell Control: Wild type mouse-cerebellum granule cell		GSE153688
Regulation		logFC: 9.51E-01 p-value: 8.19E-04
More Results	Click to View More RNA-seq Results

Thyroid Cancer [ICD-11: 2D10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[33]
Responsed Disease	Papillary thyroid cancer [ICD-11: 2D10.1]
Target Regulation	Down regulation
Pathway Response	NF-kappa B signaling pathway			hsa04064
In-vitro Model	TPC-1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
	Nthy-ori 3-1	Normal	Homo sapiens	CVCL_2659
	KTC-1	Thyroid carcinoma	Homo sapiens	CVCL_6300
	B-CPAP	Thyroid gland carcinoma	Homo sapiens	CVCL_0153
In-vivo Model	For xenograft models, 5 × 10⁶ BCPAP or KTC-1 cells from each group were injected subcutaneously into the flanks of female BALB/c nude mice (4-6 weeks old, Shanghai SLAC Laboratory Animal, China, n = 5 per group) in a volume of 150 uL PBS. Tumor growth was measured with a digital caliper every 4 days and calculated using the following formula: (length × width2)/2. To study the effect of IL-8 on tumor growth in vivo, scramble or shMETTL3 BCPAP cells were implanted hypodermically into BALB/c nude mice (2 × 10⁶ cells in 150 uL PBS, n = 10 per group). When palpable tumors formed on day 14, mice were treated with DMSO or the IL-8 inhibitor SB225002 (10 mg/kg) by intraperitoneal injection 3 times per week for 3 weeks. Six weeks post-injection, the mice were sacrificed, and the tumors were collected to analyze the frequency of TANs by flow cytometry. For the lung metastasis model, BCPAP and KTC-1 cells (2 × 10⁶ cells in 100 uL PBS) with the corresponding vectors were injected into the tail veins of BALB/c nude mice. Eight weeks after injection, the mice were euthanized, and metastatic lung nodules were analyzed (n = 5 for each group).
Response Summary	METTL3 played a pivotal tumor-suppressor role in papillary thyroid cancer carcinogenesis through Proto-oncogene c-Rel (c-Rel) and RelA inactivation of the nuclear factor Kappa-B (NF-Kappa-B) pathway by cooperating with YTHDF2 and altered TAN infiltration to regulate tumor growth.

Signal transducer and activator of transcription 3 (STAT3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	GSC11 cell line	Homo sapiens
Treatment: siYTHDF2 GSC11 cells Control: siControl GSC11 cells		GSE142825
Regulation		logFC: -6.33E-01 p-value: 6.04E-06
More Results	Click to View More RNA-seq Results

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[16]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Down regulation
Pathway Response	JAK-STAT signaling pathway			hsa04630
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	OS3 [Human osteosarcoma]	Osteosarcoma	Homo sapiens	CVCL_F866
	OS2 [Human osteosarcoma]	Osteosarcoma	Homo sapiens	CVCL_F865
	OS1 [Human osteosarcoma]	Osteosarcoma	Homo sapiens	CVCL_F864
	KHOS/NP	Osteosarcoma	Homo sapiens	CVCL_2546
Response Summary	ALKBH5 inactivated Signal transducer and activator of transcription 3 (STAT3) pathway by increasing SOCS3 expression via an m6A-YTHDF2-dependent manner. Reducing m6A mRNA levels in human osteosarcoma cells through ALKBH5 up-regulation lead to cell proliferation inhibition, cell apoptosis and cycle arrest.

Transcription factor p65 (RELA)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	GSC11 cell line	Homo sapiens
Treatment: siYTHDF2 GSC11 cells Control: siControl GSC11 cells		GSE142825
Regulation		logFC: 6.31E-01 p-value: 1.53E-07
More Results	Click to View More RNA-seq Results

Thyroid Cancer [ICD-11: 2D10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[33]
Responsed Disease	Papillary thyroid cancer [ICD-11: 2D10.1]
Target Regulation	Down regulation
Pathway Response	NF-kappa B signaling pathway			hsa04064
In-vitro Model	TPC-1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
	Nthy-ori 3-1	Normal	Homo sapiens	CVCL_2659
	KTC-1	Thyroid carcinoma	Homo sapiens	CVCL_6300
	B-CPAP	Thyroid gland carcinoma	Homo sapiens	CVCL_0153
In-vivo Model	For xenograft models, 5 × 10⁶ BCPAP or KTC-1 cells from each group were injected subcutaneously into the flanks of female BALB/c nude mice (4-6 weeks old, Shanghai SLAC Laboratory Animal, China, n = 5 per group) in a volume of 150 uL PBS. Tumor growth was measured with a digital caliper every 4 days and calculated using the following formula: (length × width2)/2. To study the effect of IL-8 on tumor growth in vivo, scramble or shMETTL3 BCPAP cells were implanted hypodermically into BALB/c nude mice (2 × 10⁶ cells in 150 uL PBS, n = 10 per group). When palpable tumors formed on day 14, mice were treated with DMSO or the IL-8 inhibitor SB225002 (10 mg/kg) by intraperitoneal injection 3 times per week for 3 weeks. Six weeks post-injection, the mice were sacrificed, and the tumors were collected to analyze the frequency of TANs by flow cytometry. For the lung metastasis model, BCPAP and KTC-1 cells (2 × 10⁶ cells in 100 uL PBS) with the corresponding vectors were injected into the tail veins of BALB/c nude mice. Eight weeks after injection, the mice were euthanized, and metastatic lung nodules were analyzed (n = 5 for each group).
Response Summary	METTL3 played a pivotal tumor-suppressor role in papillary thyroid cancer carcinogenesis through c-Rel and Transcription factor p65 (RELA) inactivation of the nuclear factor Kappa-B (NF-Kappa-B) pathway by cooperating with YTHDF2 and altered TAN infiltration to regulate tumor growth.

Deleted in lymphocytic leukemia 2 (DLEU2/LINC00022)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Human umbilical cord blood CD34+ cells	Homo sapiens
Treatment: YTHDF2 knockdown UCB CD34+ cells Control: Wild type UCB CD34+ cells		GSE107956
Regulation		logFC: -6.80E-01 p-value: 2.37E-05
More Results	Click to View More RNA-seq Results

Esophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[34]
Responsed Disease	Esophageal squamous cell carcinoma [ICD-11: 2B70.1]
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Ubiquitination degradation
	Cell apoptosis
	Decreased G0/G1 phase
In-vitro Model	HET-1A	Normal	Homo sapiens	CVCL_3702
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
	KYSE-450	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1353
	KYSE-70	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1356
	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
In-vivo Model	The number of cells inoculated in each mouse was 4 × 10⁶, 1 × 10⁶, 2 × 10⁶ and 1 × 10⁶, respectively.
Response Summary	The elevated FTO in esophageal squamous cell carcinoma decreased m6A methylation of LINC00022 transcript, leading to the inhibition of Deleted in lymphocytic leukemia 2 (DLEU2/LINC00022) decay via the m6A reader YTHDF2.

KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Human umbilical cord blood CD34+ cells	Homo sapiens
Treatment: YTHDF2 knockdown UCB CD34+ cells Control: Wild type UCB CD34+ cells		GSE107956
Regulation		logFC: 5.92E-01 p-value: 2.94E-03
More Results	Click to View More RNA-seq Results

Laryngeal cancer [ICD-11: 2C23]

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	Laryngeal cancer [ICD-11: 2C23]
Target Regulation	Up regulation
Cell Process	Cell proliferation and metastasis
In-vitro Model	AMC-HN-8	Laryngeal squamous cell carcinoma	Homo sapiens	CVCL_5966
	HOK	Normal	Hexagrammos otakii	CVCL_YE19
	Tu 212	Head and neck squamous cell carcinoma	Homo sapiens	CVCL_4915
In-vivo Model	1 × 10⁶ (100 ul) cells of infected and uninfected by lentiviral were, respectively, injected subcutaneously into nude mice which divided randomly into scramble group and shKCNQ1OT1-1 group.
Response Summary	ALKBH5 mediates KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) expression via an m6A-YTHDF2-dependent manner and KCNQ1OT1 could directly bind to HOXA9 to further regulate the proliferation, invasion and metastasis of laryngeal squamous cell carcinoma cells.

Pvt1 oncogene (PVT1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Human umbilical cord blood CD34+ cells	Homo sapiens
Treatment: YTHDF2 knockdown UCB CD34+ cells Control: Wild type UCB CD34+ cells		GSE107956
Regulation		logFC: 8.15E-01 p-value: 1.40E-05
More Results	Click to View More RNA-seq Results

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[36]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	143B	Osteosarcoma	Homo sapiens	CVCL_2270
	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
	SaOS-LM7	Osteosarcoma	Homo sapiens	CVCL_0515
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	NHOst (Normal human osteoblast cells)
	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
In-vivo Model	Indicated stable 143B cells were subcutaneously injected into nude mice.
Response Summary	ALKBH5 decreased the m6A modification of Pvt1 oncogene (PVT1), thus inhibiting the binding of reader protein YTHDF2 in PVT1. ALKBH5-mediated PVT1 upregulation promoted the osteosarcoma cell proliferation in vitro and tumor growth in vivo.

Diabetic encephalopathy [ICD-11: 8E47]

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	Diabetic encephalopathy [ICD-11: 8E47]

Autophagy protein 5 (ATG5)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.24E+00	GSE49339

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				[37]
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagy
	Adipogenesis regulation
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
	Pig primary preadipocytes (Isolated from cervical subcutaneous adipose tissue of piglets)
In-vivo Model	Mice were maintained at 22 ± 2 ℃ with a humidity of 35 ± 5% under a 12 h light and 12 h dark cycle, with free access to water and food. For the HFD experiment, female control (Fto^flox/flox) and adipose-selective fto knockout (Fabp4-Cre Fto^flox/flox, fto-AKO) mice were fed with high-fat diet (60% fat in calories; Research Diets, D12492) for the desired periods of time, and food intake and body weight were measured every week after weaning (at 3 weeks of age).
Response Summary	Autophagy protein 5 (ATG5) and Atg7 were the targets of YTHDF2 (YTH N6-methyladenosine RNA binding protein 2). Upon FTO silencing, Atg5 and Atg7 transcripts with higher m6A levels were captured by YTHDF2, which resulted in mRNA degradation and reduction of protein expression, thus alleviating autophagy and adipogenesis.

Osteoarthritis [ICD-11: FA05]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[47]
Responsed Disease	Osteoarthritis [ICD-11: FA05]

Epidermal growth factor receptor (EGFR)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.61E+00	GSE49339

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				[38]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Down regulation
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	Glucose metabolism
In-vitro Model	BEL-7402	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	QGY-7703	Endocervical adenocarcinoma	Homo sapiens	CVCL_6715
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	5 × 10⁶ of HEP3B and SMMC7721 stable cells were resuspended in 0.1 ml of PBS and subcutaneously injected into the flank of mice.
Response Summary	YTHDF2 acts as a tumor suppressor to repress cell proliferation and growth via destabilizing the Epidermal growth factor receptor (EGFR) mRNA in HCC.

Insulin receptor substrate 1 (IRS1)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.86E+00	GSE49339

Endometrial cancer [ICD-11: 2C76]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[39]
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	T HESCs	Normal	Homo sapiens	CVCL_C464
	RL95-2	Endometrial adenosquamous carcinoma	Homo sapiens	CVCL_0505
	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293
Response Summary	YTHDF2 inhibited the proliferation and invasion of endometrial cancer(EC) via inhibiting Insulin receptor substrate 1 (IRS1) expression in m6A epigenetic way, which suggests a potential therapeutic target for EC.

MAP kinase kinase 4 (MAP2K4)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.75E+00	GSE49339

Diseases of the circulatory system [ICD-11: BE2Z]

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	Diseases of the circulatory system [ICD-11: BE2Z]
Response Summary	YTHDF2 regulates the stability of MAP kinase kinase 4 (MAP2K4) and MAP4K4 mRNAs.This study identified that dasatinib and quercetin alleviate LPS-induced senescence in HUVECs via the TRAF6-MAPK-NF-Kappa-B axis in a YTHDF2-dependent manner, providing novel ideas for clinical treatment of age-related cardiovascular diseases.

Inflammatory response [ICD-11: MG46]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[41]
Responsed Disease	Inflammatory response [ICD-11: MG46]
Target Regulation	Down regulation
Pathway Response	MAPK signaling pathway			hsa04010
In-vitro Model	RAW 264.7	Mouse leukemia	Mus musculus	CVCL_0493
Response Summary	YTHDF2 knockdown increases mRNA expression levels of MAP kinase kinase 4 (MAP2K4) and MAP4K4 via stabilizing the mRNA transcripts, which activate MAPK and NF-Kappa-B signaling pathways, which promote the expression of proinflammatory cytokines and aggravate the inflammatory response in LPS-stimulated RAW 264.7 cells.

PI3-kinase subunit beta (PIK3CB)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.28E+00	GSE49339

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				[42]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Responsed Drug	AZD6482		Terminated	Drug Info
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glucose metabolism
In-vitro Model	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
In-vivo Model	Established cohorts of mice bearing tumour xenografts driven by PTEN-deficient BxPC-3 and PANC-1 cells with PIK3CB overexpression. When tumours grew to ~300 mm³, mice were grouped and administered with vehicle (DMSO) or KIN-193 via intraperitoneal injection (20 mg/kg) once daily.
Response Summary	N6-methyladenosine mRNA methylation of PIK3CB regulates AKT signalling to promote PTEN-deficient pancreatic cancer progression. Rs142933486 is significantly associated with the overall survival of PDAC by reducing the PIK3CB m6A level, which facilitated its mRNA and protein expression levels mediated by the m6A 'writer' complex (METTL13/METTL14/WTAP) and the m6A 'reader' YTHDF2. KIN-193, a PI3-kinase subunit beta (PIK3CB)-selective inhibitor, is shown to serve as an effective anticancer agent for blocking PTEN-deficient PDAC.

T-cell acute lymphocytic leukemia protein 1 (TAL1)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.17E+00	GSE49339

Hematological disorders [ICD-11: 3C0Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[43]
Responsed Disease	Hematological disorders [ICD-11: 3C0Z]
Target Regulation	Down regulation
Cell Process	RNA stability
In-vitro Model	Hematopoietic stem cells (Hematopoietic stem cells)
In-vivo Model	For the rescue experiment, LSK cells were sorted from wt and Ythdf2 KO mouse BM and cultured overnight in StemSpan SFEM medium (Stem Cell Technologies) supplemented with 10 ug/mL heparin (Sigma), 0.5 × penicillin/streptomycin (Sigma), 10 ng/mL recombinant mouse (rm) stem cell factor (SCF), and 20 ng/mL Tpo 75 at 37 ℃ in a 5% CO2 5% O2 atmosphere.
Response Summary	Knocking down one of YTHDF2's key targets, T-cell acute lymphocytic leukemia protein 1 (TAL1) mRNA, partially rescued the phenotype.the function of YTHDF2 in adult stem cell maintenance and identifies its important role in regulating HSC ex vivo expansion.

TNF alpha-induced protein 3 (TNFAIP3)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.94E+00	GSE49339

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				[4]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Responsed Drug	Temozolomide		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	RNA stability
In-vitro Model	T98G	Glioblastoma	Homo sapiens	CVCL_0556
In-vitro Model	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
In-vivo Model	5 × 10⁶ infected T98G cells (LV-NC or LV-YTHDF2) were injected into the flanks of mice through subcutaneous.
Response Summary	YTHDF2 enhanced TMZ resistance in GBM by activation of the PI3K/Akt and NF-Kappa-B signalling pathways via inhibition of EPHB3 and TNF alpha-induced protein 3 (TNFAIP3).

Lupus erythematosus [ICD-11: 4A40]

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	Lupus erythematosus [ICD-11: 4A40]
Target Regulation	Up regulation
Cell Process	Immunity
In-vitro Model	PBMCs (Human peripheral blood mononuclear cells (PBMCs) are isolated from peripheral blood and identified as any blood cell with a round nucleus)
Response Summary	MiR-19a regulated TNF alpha-induced protein 3 (TNFAIP3) degradation by downregulating the expression of YTH N6-methyladenosine RNA-binding protein 2 (YTHDF2). The circGARS sponges miR-19a to regulate YTHDF2 expression to promote SLE progression through the A20/NF-Kappa-B axis and acts as an independent biomarker to help the treatment of SLE patients.

FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.55E+00	GSE49339

Endometrial cancer [ICD-11: 2C76]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[19]
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulation	Down regulation
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	HEC-1-B	Endometrial adenocarcinoma	Homo sapiens	CVCL_0294
Response Summary	YTHDF2-mediated LncRNA FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) degradation promotes cell proliferation by elevating SOX4 expression in endometrioid endometrial carcinoma.

6-phosphogluconate dehydrogenase, decarboxylating (6PGD/PGD)

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				[45]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulation	Up regulation
Pathway Response	Pentose phosphate pathway			hsa00030
Cell Process	Cell growth
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	HEK293T	Normal	Homo sapiens	CVCL_0063
Response Summary	YTHDF2 directly binds to the m6A modification site of 6-phosphogluconate dehydrogenase, decarboxylating (6PGD/PGD) three prime untranslated region (3'-UTR) to promote 6PGD mRNA translation in lung cancer cells.

ATP-binding cassette sub-family C member 10 (ABCC10)

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				[46]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Gefitinib		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	ABC transporters			hsa02010
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
In-vivo Model	Mice were randomized into three groups (n = 7/group), 1 × 10⁷ PC9 cells absorbed exosomes were subcutaneously injected into the Bilateral groin of mice. Treatment began 1 week following injection, the mice were intraperitoneally injected with gefitinib (30 mg/kg/day).
Response Summary	Not only FTO knockdown enhanced the gefitinib sensitivity of GR cells but also FTO reduction in donor exosomes alleviated the acquired resistance of recipient non-small cell lung cancer PC9 cells. FTO/YTHDF2/ATP-binding cassette sub-family C member 10 (ABCC10) axis played a role in intercellular transmission of GR cell-derived exosome-mediated gefitinib resistance.

Axin-1 (AXIN1)

Target Gene

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[48]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Ect1/E6E7	Normal	Homo sapiens	CVCL_3679
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
Response Summary	YTHDF2 interference could suppress the EMT of cervical cancer cells and enhance cisplatin chemosensitivity by regulating Axin-1 (AXIN1).

Parkinson disease [ICD-11: 8A00]

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	Parkinson disease [ICD-11: 8A00]

Bax inhibitor 1 (TMBIM6)

Target Gene

Pre-eclampsia [ICD-11: JA24]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[50]
Responsed Disease	Pre-eclampsia [ICD-11: JA24]
Target Regulation	Down regulation
In-vitro Model	HTR-8/SVneo	Normal	Homo sapiens	CVCL_7162

BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)

Target Gene

Sepsis [ICD-11: 1G40]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[52]
Responsed Disease	Sepsis [ICD-11: 1G40]
In-vivo Model	To assess mortality rates, mice were intraperitoneally administered LPS (30 mg/kg), with mdivi (3 mg/kg) given intraperitoneally 1 h before LPS challenge and then continued for 3 consecutive days. The 72-h mortality was subsequently recorded. For evaluating heart injury, mice received an injection of LPS (10 mg/kg), with songorine (10 or 50 mg/kg) administered 1 h before and 12 h after LPS treatment. Mice were euthanized 24 h later for heart collection.

Osteoarthritis [ICD-11: FA05]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[47]
Responsed Disease	Osteoarthritis [ICD-11: FA05]

Injury of heart [ICD-11: NB31]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[53]
Responsed Disease	Myocardial injury [ICD-11: NB31.Z]
Target Regulation	Down regulation
In-vitro Model	H9c2(2-1)	Normal	Rattus norvegicus	CVCL_0286
In-vivo Model	All rats were arranged into 4 groups, with 10 rats in each group: sham, IR, IR + adeno-associated virus-mediated YTHDF2 overexpression vector (AAV-YTHDF2), and IR + negative control of AAV-YTHDF2 (AAV-NC) groups. Rats in the sham group underwent the same procedure without ligation. Rats in the IR group experienced 30-min ischemia and then 24-h reperfusion.

Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2)

Target Gene

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				[54]
Responsed Disease	Azoospermia [ICD-11: GB04.0]
Target Regulation	Down 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 PPM1A (protein phosphatase 1A, magnesium dependent, alpha isoform), a negative AMP-activated protein kinase (AMPK) regulator, but decreased expression of Calcium/calmodulin-dependent protein kinase kinase 2 (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. knock down of YTHDF2 increased expression of Camkk2 at both mRNA and protein levels to a similar extent as knock down of METTL14 in both TM3 cells and primary LCs.

Cellular tumor antigen p53 (TP53/p53)

Target Gene

Melanoma of uvea [ICD-11: 2D0Y]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[55]
Responsed Disease	Melanoma of uvea [ICD-11: 2D0Y]
In-vitro Model	OCM-1	Amelanotic melanoma	Homo sapiens	CVCL_6934
In-vitro Model	CRMM-1	Conjunctival melanoma	Homo sapiens	CVCL_M593

Cyclic AMP-dependent transcription factor ATF-4 (ATF4)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 6 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Asparagine inhibitor		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Chloroquine		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 3 Reporting the m6A-centered Disease Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Meclofenamate sodium		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 4 Reporting the m6A-centered Disease Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Rapamycin		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 5 Reporting the m6A-centered Disease Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	CB-839		Phase 2	Drug Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 6 Reporting the m6A-centered Disease Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	GLS-IN-968		Investigative	Drug Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition.

Cyclic-AMP-dependent transcription factor ATF-3 (ATF3)

Target Gene

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[57]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Down regulation
In-vitro Model	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
Response Summary	The increased expression of Cyclic-AMP-dependent transcription factor ATF-3 (ATF3) in tamoxifen-resistant cells arises from the decreased expression of the m6A reader protein YTHDF2 and the ensuing elevated stability of ATF3 mRNA, which ultimately promotes the translation of ATF3. ATF3 as a candidate therapeutic target for mitigating drug resistance in breast cancer cells.

Cyclin-A2 (CCNA2)

Target Gene

Obesity [ICD-11: 5B81]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[58]
Responsed Disease	Obesity [ICD-11: 5B81]
Responsed Drug	Epigallocatechin gallate		Phase 3	Drug Info
Target Regulation	Down regulation
Cell Process	Adipogenesis
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Response Summary	m6A-dependent Cyclin-A2 (CCNA2) and CDK2 expressions mediated by FTO and YTHDF2 contributed to EGCG-induced adipogenesis inhibition.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[59]
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Adipogenesis
	Arrest cell cycle at S phase
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Response Summary	FTO knockdown markedly decreased the expression of Cyclin-A2 (CCNA2) and CDK2, crucial cell cycle regulators, leading to delayed entry of MDI-induced cells into G2 phase. m6A-binding protein YTHDF2 recognized and decayed methylated mRNAs of CCNA2 and CDK2, leading to decreased protein expression, thereby prolonging cell cycle progression and suppressing adipogenesis. The adipocyte life cycle, including proliferation and adipogenesis, has become a potential target for many bioactive compounds and drugs for the prevention and treatment of obesity.

Cyclin-dependent kinase 2 (CDK2)

Target Gene

Obesity [ICD-11: 5B81]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[58]
Responsed Disease	Obesity [ICD-11: 5B81]
Responsed Drug	Epigallocatechin gallate		Phase 3	Drug Info
Target Regulation	Down regulation
Cell Process	Adipogenesis
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Response Summary	m6A-dependent CCNA2 and Cyclin-dependent kinase 2 (CDK2) expressions mediated by FTO and YTHDF2 contributed to EGCG-induced adipogenesis inhibition.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[59]
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Adipogenesis
	Arrest cell cycle at S phase
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Response Summary	FTO knockdown markedly decreased the expression of CCNA2 and Cyclin-dependent kinase 2 (CDK2), crucial cell cycle regulators, leading to delayed entry of MDI-induced cells into G2 phase. m6A-binding protein YTHDF2 recognized and decayed methylated mRNAs of CCNA2 and CDK2, leading to decreased protein expression, thereby prolonging cell cycle progression and suppressing adipogenesis. The adipocyte life cycle, including proliferation and adipogenesis, has become a potential target for many bioactive compounds and drugs for the prevention and treatment of obesity.

Retinopathy [ICD-11: 9B71]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[61]
Responsed Disease	Diabetic retinopathy [ICD-11: 9B71.0]
Responsed Drug	FB23-2	Investigative	Drug Info
Target Regulation	Down regulation

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

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				[62]
Responsed Disease	Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell proliferation
	Arrest cell cycle at G0/G1 phase
In-vitro Model	HuCC-T1	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_0324
	RBE	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_4896
	HCCC-9810 (The intrahepatic cholangiocarcinoma cell lines (HCCC-9810) were purchased from Cellcook Co., Ltd. (Guangzhou, China).)
	HIBEC (The normal intrahepatic bile duct cell line (HIBEC) were purchased from Cellcook Co., Ltd. (Guangzhou, China).)
In-vivo Model	For tumour xenograft models, 1 × 10⁷ HuCC-T1 cells in knockdown group or control group were implanted into the right flank of 5-week-old female nude mice. The volumes of tumour were recorded every 4 days by calliper. The volumes were calculated as length × width2/2. For patient-derived xenograft (PDX) model (PDX0075), ICC tissues from a patient, who relapsed in 6 months after R0 resection and subsequent chemotherapy with cisplatin and gemcitabine, were diced into 3 mm³ pieces and transplanted subcutaneously into the right flank of 5-week-old female B-NDG mice.
Response Summary	The role of YTHDF2 in tumourigenesis and cisplatin-desensitising function by promoting the degradation of Cyclin-dependent kinase inhibitor 1B (CDKN1B/p27) mRNA in an m6 A-dependent manner. YTHDF2 exhibits tumour oncogenic and cisplatin-desensitising properties, which offer insight into the development of novel combination therapeutic strategies for intrahepatic cholangiocarcinoma.

Cyclin-dependent kinase inhibitor 2A (CDKN2A)

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				[63]
Responsed Disease	Renal cell carcinoma [ICD-11: 2C90]
Target Regulation	Down regulation
Cell Process	RNA stability
In-vitro Model	UOK120	Papillary renal cell carcinoma	Homo sapiens	CVCL_B099
	UOK109	Renal cell carcinoma	Homo sapiens	CVCL_B087
	HK-2 [Human kidney]	Normal	Homo sapiens	CVCL_0302
	HEK293T	Normal	Homo sapiens	CVCL_0063
	ACHN	Papillary renal cell carcinoma	Homo sapiens	CVCL_1067
	786-O	Renal cell carcinoma	Homo sapiens	CVCL_1051
In-vivo Model	The mice were subcutaneously inoculated with 786-O cells stably transfected with lentiviruses carrying sh-NC/sh-circMET, respectively (5 × 10⁶, 200 uL).
Response Summary	CircMET enhances mRNA decay of Cyclin-dependent kinase inhibitor 2A (CDKN2A) by direct interaction and recruitment of YTHDF2. CircMET promotes the development of NONO-TFE3 tRCC, and the regulation to both CDKN2A and SMAD3 of circMET was revealed.

Cystathionine beta-synthase (CBS)

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				[64]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Proteasome pathway degradation
In-vitro Model	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
	MKN28	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_1416
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	GSE-1 (Gse-1 is a human gastric epithelial cell line)
	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
Response Summary	CBSLR interacted with YTHDF2 to form a CBSLR/YTHDF2/CBS signaling axis that decreased the stability of Cystathionine beta-synthase (CBS) mRNA by enhancing the binding of YTHDF2 with the m6A-modified coding sequence (CDS) of CBS mRNA. Reveal a novel mechanism in how HIF1-Alpha/CBSLR modulates ferroptosis/chemoresistance in GC, illuminating potential therapeutic targets for refractory hypoxic tumors.

Cystine/glutamate transporter (SLC7A11)

Target Gene

Atherosclerosis [ICD-11: BD40]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[65]
Responsed Disease	Atherosclerosis [ICD-11: BD40.Z]
Target Regulation	Down regulation
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959

Injury of heart [ICD-11: NB31]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[66]
Responsed Disease	Myocardial injury [ICD-11: NB31.Z]
Target Regulation	Down regulation
In-vitro Model	H9c2(2-1)	Normal	Rattus norvegicus	CVCL_0286

Death-associated protein kinase 3 (DAPK3)

Target Gene

Gallbladder cancer [ICD-11: 2C13]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[67]
Responsed Disease	Gallbladder cancer [ICD-11: 2C13]
Responsed Drug	Gemcitabine	Approved	Drug Info
Target Regulation	Down regulation
In-vivo Model	Male BALB/c nude mice (6 weeks old) were used for xenograft experiments. A 150 μL-cell suspension containing 5 × 10⁶ cells was injected s.c. into each nude mouse. Tumor volumes were measured every 4 days for 1 month. To evaluate chemosensitivity to gemcitabine, mice were i.p. injected with gemcitabine (50 mg/kg) every 4 days when the tumor volume reached 100 mm3.Male NOD/SCID mice (6 weeks old) were used for lung metastasis experiments. A 150 μL-cell suspension containing 5 × 10⁵ cells was injected i.v. into the tail vein of each mouse. After 1 month, the lungs were harvested and photographed, and the number of metastatic lesions was calculated.

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

Target Gene

Intervertebral disc degeneration [ICD-11: FA80]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[68]
Responsed Disease	Intervertebral disc degeneration [ICD-11: FA80]
Target Regulation	Down regulation

DNA replication licensing factor MCM5 (MCM5)

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				[69]
Responsed Disease	Liver hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	OSMI-1		Investigative	Drug Info
Target Regulation	Up regulation
In-vitro Model	HepAD38	Hepatoblastoma	Homo sapiens	CVCL_M177
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	HEK293	Normal	Homo sapiens	CVCL_0045
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	For the xenograft implantation model, 2 × 10⁶ MHCC-97H cells were subcutaneously injected into the flank of nude mice.

DNA-binding protein inhibitor ID-2 (ID2)

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				[70]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	SW1990	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	CFPAC-1	Cystic fibrosis	Homo sapiens	CVCL_1119
	HPDE6c7	Normal	Homo sapiens	CVCL_0P38
	Panc02	Mouse pancreatic ductal adenocarcinoma	Mus musculus	CVCL_D627
In-vivo Model	For the subcutaneous tumor model, cells from the treatment group and the control group (1 × 10⁷) were subcutaneously injected into the right groin of BALB/c nude mice (4-6 weeks old, 18-20 g, 4 mice each). Both the treatment group and control group had 5 BALB/c nude mice each. After 21 days, all mice were sacrificed and tumor volume and weight were measured. For the pancreatic cancer in situ tumor model, mice were anesthetized with Avertin at a dose of 0.2 ml/10 g body weight, and 5 × 10⁵ panc2 treatment group cells and control group cells were injected into the pancreas of mice respectively, and the abdomen was closed for disinfection. Both the treatment group and control group had 5 C57 mice each. After 21 days, the mice were sacrificed, the in-situ tumor was removed, and the volume and weight were measured for subsequent experiments.

E3 ubiquitin-protein ligase SMURF1 (SMURF1)

Target Gene

Inflammatory response [ICD-11: MG46]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[10]
Responsed Disease	Inflammatory response [ICD-11: MG46]
Target Regulation	Down regulation
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	RNA stability
In-vitro Model	MC3T3-E1	Normal	Mus musculus	CVCL_0409
Response Summary	METTL3 knockdown inhibits osteoblast differentiation and Smad-dependent signaling by stabilizing Smad7 and E3 ubiquitin-protein ligase SMURF1 (SMURF1) mRNA transcripts via YTHDF2 involvement and activates the inflammatory response by regulating MAPK signaling in LPS-induced inflammation.

ELAV-like protein 1 (HuR/ELAVL1)

Target Gene

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[71]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Down regulation
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
In-vivo Model	A total of 1 × 10⁶ PC3 cells or DU145 cells suspended in a mixture of 100 uL PBS and Matrigel were subcutaneously injected into BALB/c nude mice. Tumor weight were measured 2 months after the engraftment. To evaluate the role of METTL3 in tumor metastasis, PC3 cells with or without knockdown of METTL3 were injected into SCID mice through the tail vein (1 × 10⁶ cells per mouse). After eight weeks, mice were sacrificed and their lung tissues were collected for subsequent analyses.
Response Summary	m6A modification levels were markedly upregulated in human PCa tissues due to increased expression of METTL3. METTL3 mediates m6A modification of USP4 mRNA at A2696, and m6A reader protein YTHDF2 binds to and induces degradation of USP4 mRNA by recruiting RNA-binding protein HNRNPD to the mRNA. Decrease of USP4 fails to remove the ubiquitin group from ELAV-like protein 1 (HuR/ELAVL1) protein, resulting in a reduction of ELAVL1 protein. Lastly, downregulation of ELAVL1 in turn increases ARHGDIA expression, promoting migration and invasion of PCa cells.

Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1)

Target Gene

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

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[72]
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Responsed Drug	Rapamycin	Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	Rapamycin inhibited FTO activity, and directly targeted Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) transcripts and mediated their expression in an m6A-dependent manner in oral squamous cell carcinoma. After FTO silencing, YTHDF2 captured eIF4G1 transcripts containing m6A, resulting in mRNA degradation and decreased expression of eIF4G1 protein, thereby promoting autophagy and reducing tumor occurrence.

Forkhead box protein O1 (FOXO1)

Target Gene

Female infertility [ICD-11: GA31]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[73]
Responsed Disease	Female infertility [ICD-11: GA31]
Target Regulation	Down regulation
In-vitro Model	T HESCs	Normal	Homo sapiens	CVCL_C464
	HTR-8/SVneo	Normal	Homo sapiens	CVCL_7162
	HTR-8	Normal	Homo sapiens	CVCL_D728
In-vivo Model	Five female mice were subjected to a normal pregnancy assay. Uterine tissues of 14 female donor mice were cut up and injected into the abdominal cavity of 28 female recipient mice. After 21 d, 10 male C57 mice were mated with the recipient mice, and the next day, when vaginal plugs were observed, was regarded as day 1. Eight recipient mice were euthanized by cervical dislocation after deep pentobarbital anesthesia on day 8, and the number of blastocysts in the uterus was counted. At the night of day 3, 10 μL of STM2457, a METTL3 inhibitor (Sellcek, S9870, 10 μM) and 10 μL dimethyl sulfoxide (DMSO) were individually injected into the uterine horns of 20 recipient mice. The mice were euthanized on day 8, and the number of blastocysts in the uterus was counted. The uterine tissues were collected and fixed in 4% (w/v) paraformaldehyde for histological and IHC analyses.

Forkhead box protein O3 (FOXO3)

Target Gene

Intervertebral disc degeneration [ICD-11: FA80]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[74]
Responsed Disease	Intervertebral disc degeneration [ICD-11: FA80]
Target Regulation	Down regulation

Glucose transporter type 1 (GLUT1)

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		[75]
Responsed Disease	Liver hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Down regulation
In-vivo Model	Male BALB/c nude mice (aged 4-6 weeks; n = 5/group) were obtained from Vital River Laboratory Animal Technology (Beijing, China). MHCC97H or Huh7 cells (2 × 10⁶ cells/mouse) stably transfected with lentivirus containing different plasmids in 100 μL DMEM were subcutaneously or orthotopically implanted into the nude mice.

Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[76]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
In-vitro Model	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In-vitro Model	RKO	Colon carcinoma	Homo sapiens	CVCL_0504

Histone deacetylase 4 (HDAC4)

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		[77]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulation	Up regulation

Histone-lysine N-methyltransferase EHMT2 (G9a)

Target Gene

Pain disorders [ICD-11: 8E43]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[78]
Responsed Disease	Neuropathic pain [ICD-11: 8E43.0]
Target Regulation	Down regulation

Histone-lysine N-methyltransferase EZH2 (EZH2)

Target Gene

Endometriosis [ICD-11: GA10]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[79]
Responsed Disease	Endometriosis [ICD-11: GA10]
Target Regulation	Down regulation

HPK/GCK-like kinase HGK (MAP4K4)

Target Gene

Diseases of the circulatory system [ICD-11: BE2Z]

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	Diseases of the circulatory system [ICD-11: BE2Z]
Response Summary	YTHDF2 regulates the stability of MAP2K4 and HPK/GCK-like kinase HGK (MAP4K4) mRNAs.This study identified that dasatinib and quercetin alleviate LPS-induced senescence in HUVECs via the TRAF6-MAPK-NF-Kappa-B axis in a YTHDF2-dependent manner, providing novel ideas for clinical treatment of age-related cardiovascular diseases.

Inflammatory response [ICD-11: MG46]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[41]
Responsed Disease	Inflammatory response [ICD-11: MG46]
Target Regulation	Down regulation
Pathway Response	MAPK signaling pathway			hsa04010
In-vitro Model	RAW 264.7	Mouse leukemia	Mus musculus	CVCL_0493
Response Summary	YTHDF2 knockdown increases mRNA expression levels of MAP2K4 and HPK/GCK-like kinase HGK (MAP4K4) via stabilizing the mRNA transcripts, which activate MAPK and NF-Kappa-B signaling pathways, which promote the expression of proinflammatory cytokines and aggravate the inflammatory response in LPS-stimulated RAW 264.7 cells.

Integrin beta-1 (ITGB1)

Target Gene

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

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[80]
Responsed Disease	Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Target Regulation	Down regulation
In-vitro Model	HO-8910	Endocervical adenocarcinoma	Homo sapiens	CVCL_6868
In-vitro Model	A2780	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
In-vivo Model	We injected 8 × 10⁵ HO8910 cells into the footpads of mice. The mice were randomized two weeks after tumor cell injection to receive either an ITGB1 blocking antibody (Santa, CA, USA) or an IgG isotype antibody twice per week for four weeks 22,23. Y15 (30 mg/kg) against p-FAK (Tyr397) and PBS as a control were intraperitoneally injected twice per week for four weeks in the FAK-treatment assays. The main tumors and popliteal LNs were harvested and fixed in paraformaldehyde after six weeks of tumor cell inoculation. LN volumes were calculated as follows: LN volume (mm3) = (length [mm]) × (width [mm])2 × 0.52. The formalin-fixed, paraffin-embedded samples were analysed using immunohistochemistry and haematoxylin and eosin (H&E) staining.

Retinopathy [ICD-11: 9B71]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[81]
Responsed Disease	Diabetic retinopathy [ICD-11: 9B71.0]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway	hsa04151
Cell Process	RNA stability
In-vitro Model	RMECs (Retinal microvascular endothelial cells (RMECs) purchased from Olaf (Worcester, MA, USA))
	rMCs (Retinal Muller cells (rMCs) from Kerafast Inc. (Boston, MA))
In-vivo Model	Male mice (8-10 weeks old, SLAC Laboratory Animal Co., Ltd., Shanghai, China) were administrated with STZ through intraperitoneal injection (I.P) for continuous 5 days (d).
Response Summary	KAT1 triggers YTHDF2-mediated Integrin beta-1 (ITGB1) mRNA instability to alleviate the progression of DR.

Interferon regulatory factor 1 (Irf1)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[82]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 10⁶ CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Stat1 and Interferon regulatory factor 1 (Irf1) mRNA via Ythdf2.

Interferon regulatory factor 3 (IRF3)

Target Gene

Picornavirus infections presenting in the skin or mucous membranes [ICD-11: 1F05]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[83]
Responsed Disease	Picornavirus infections presenting in the skin or mucous membranes [ICD-11: 1F05.3]
In-vitro Model	PK-15	N.A.	Sus scrofa	CVCL_2160
	HT-29	Colon adenocarcinoma	Homo sapiens	CVCL_0320
	IB-RS-2	N.A.	Sus scrofa	CVCL_4528
	CPTC-SVIL-1	N.A.	Oryctolagus cuniculus	CVCL_C2LN
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BHK-21	N.A.	Mesocricetus auratus	CVCL_1914
	RD	Embryonal rhabdomyosarcoma	Homo sapiens	CVCL_1649

Interleukin-11 (IL11)

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				[27]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Down regulation
Pathway Response	HIF-1 signaling pathway			hsa04066
Cell Process	Biological regulation
In-vitro Model	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
In-vitro Model	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	A number of 5 × 10⁶ SMMC7721 or MHCC97H cells re-suspended in 100 uL of PBS were subcutaneously injected into the right flank of 6-week old male NCG mice.
Response Summary	YTHDF2 processed the decay of m6A-containing Interleukin-11 (IL11) and serpin family E member 2 (SERPINE2) mRNAs. YTHDF2 transcription succumbed to hypoxia-inducible factor-2-alpha (HIF-2-alpha). Administration of a HIF-2-alpha antagonist (PT2385) restored YTHDF2-programed epigenetic machinery and repressed liver cancer.

Metalloproteinase inhibitor 3 (TIMP3)

Target Gene

Intervertebral disc degeneration [ICD-11: FA80]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[84]
Responsed Disease	Intervertebral disc degeneration [ICD-11: FA80]
In-vitro Model	Pten-/- P2	Carcinoma of the mouse prostate gland	Mus musculus	CVCL_VQ83
In-vivo Model	We also used surgery to cause spine instability in rats to observe IVD changes under abnormal stress (Figure 1f). X-ray scans 6 months after surgery showed that the lumbar vertebral sequence line was continuous, with no stenosis in various intervertebral foramen in the ctrl group.

Mothers against decapentaplegic homolog 2 (SMAD2)

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	Lung cancer [ICD-11: 2C25]
Target Regulation	Down regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Response Summary	YTHDF2 inhibits the migration and invasion of lung adenocarcinoma cells by regulating the FAM83D-TGFbeta1-Mothers against decapentaplegic homolog 2 (SMAD2) pathway, which will play an important role in lung cancer metastasis.

Mutated in multiple advanced cancers 1 (PTEN)

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		[86]
Responsed Disease	Brain cancer [ICD-11: 2A00]
Target Regulation	Down regulation

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		[87]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation

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		[88]
Responsed Disease	Pulmonary hypertension due to lung disease or hypoxia [ICD-11: BB01.2]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway	hsa04151
Cell Process	Cell apoptosis
In-vitro Model	PASMC cell line (Pulmonary artery smooth muscle cell)
In-vivo Model	10 rats were divided into control and HPH group. In detail, 5 rats of the hypoxia groups were exposed to hypoxia (10%O₂) chamber (AiPu XBS-02B, China) for 4 weeks. In addition, 5 rats of control group were kept under normoxic conditions (21% O₂) for 4 weeks. Rats were housed in standard polypropylene cages under controlled photocycle (12 h light/12 h dark) under 22-25 ℃ temperature.
Response Summary	METTL3/YTHDF2/Mutated in multiple advanced cancers 1 (PTEN) axis exerts a significant role in hypoxia induced PASMCs proliferation, providing a novel therapeutic target for hypoxic pulmonary hypertension.

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

Target Gene

Lung cancer [ICD-11: 2C25]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[89]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Responsed Drug	Gefitinib		Approved	Drug Info
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
	PC-9/GR2	Lung adenocarcinoma	Homo sapiens	CVCL_DI29
	HCC827/GR	N.A.	Homo sapiens	CVCL_E7R9
In-vivo Model	To establish xenograft models, five-week-old male mice were orthotopically injected with the same number of the PC9/GR cells. Tumours had developed after 4 days, at which time the xenografted mice were randomly divided into the following two experimental groups (each group with 6 mice): (1) the control group and (2) the gefitinib group.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[89]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulation	Up regulation

Rheumatoid arthritis [ICD-11: FA20]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[90]
Responsed Disease	Rheumatoid arthritis [ICD-11: FA20]
Target Regulation	Down regulation

NAD-dependent protein deacetylase sirtuin-1 (SIRT1)

Target Gene

Endometriosis [ICD-11: GA10]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[91]
Responsed Disease	Endometriosis [ICD-11: GA10]
Target Regulation	Down regulation
In-vivo Model	For in vivo studies, the shMETTL3 sequence was subcloned into adeno-associated virus (AAV) construct 9 (AAV9). Recombinant AAV9 was manufactured by GenePharma (Shanghai, China). The ectopic endometrium was obtained from a 28-year-old woman who had undergone an operation for ovarian endometriosis. The tissue sample was washed twice with PBS and cut into three 3- to 5-mm pieces, and suspended by PBS.he animals were administered intraperitoneal injections of 30 mg/kg 17-oestradiol every three days after the endometrial injections. Xenografts were generated under bilateral axillae after 14 days with tumour volumes of approximately 10 mm3.

Neurogenic locus notch homolog protein 1 (NOTCH1)

Target Gene

Aortic aneurysm or dissection [ICD-11: BD50]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[92]
Responsed Disease	Thoracic aortic dissection [ICD-11: BD50.3]
Target Regulation	Down regulation

Nuclear factor erythroid 2-related factor 2 (NFE2L2)

Target Gene

Epilepsy due to structural or metabolic conditions or diseases [ICD-11: 8A60]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[93]
Responsed Disease	Epilepsy due to structural or metabolic conditions or diseases [ICD-11: 8A60.5]
Target Regulation	Down regulation

Acute ischemic stroke [ICD-11: 8B11]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[94]
Responsed Disease	Acute ischemic stroke [ICD-11: 8B11]
Target Regulation	Down regulation
In-vitro Model	SH-SY5Y	Neuroblastoma	Homo sapiens	CVCL_0019
In-vivo Model	Cerebral I/R injury was induced by MCAO/R surgery following previous method [10]. Rats were anesthetized by intraperitoneal injection of 2% sodium pentobarbital. After cutting the cervical skin of the rats with surgical scissors, the internal, external and common carotid arteries were separated. Then the proximal ends of the external and the common carotid arteries were ligated and the distal internal carotid artery was clipped. After cutting an incision 1 cm away from the bifurcation of the internal carotid artery with a surgical scissors, the left common carotid artery was slowly inserted into the internal carotid artery of the rats with sutures coated with silicone (head diameter 0.36±0.02 mm, Beijing Sunbio Biotech Co., Ltd., China) until sutures reached the bifurcation of the middle cerebral artery, and the wound was sutured after the sutures were fixed. After blocking blood flow for 1 h, the plug was removed to restore blood flow and reperfusion was performed. Other rats were selected for the Sham group, and the operation procedure was the same as above except for no ligation and insertion.

Reproductive System disorders [ICD-11: SM9Z-SN0Z]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[95]
Responsed Disease	Reproductive System disorders [ICD-11: SM9Z-SN0Z]
Target Regulation	Up regulation
In-vitro Model	TM3	Normal	Mus musculus	CVCL_4326

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

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				[96]
Responsed Disease	Glioma [ICD-11: 2A00.0]
Target Regulation	Up regulation
Pathway Response	NF-kappa B signaling pathway			hsa04064
In-vitro Model	U87 (A primary glioblastoma cell line)
	N33 (The GBM patient-derived cell line)
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	H4	Astrocytoma	Homo sapiens	CVCL_1239
In-vivo Model	Five-week-old female BALB/c nude mice (Charles Rivers, Beijing, China) were selected for the experiments. U87 cells (5 × 10⁵) transfected with an empty vector, YTHDF2 overexpression, or METTL3 overexpression vectors were suspended in PBS and injected into the right frontal node of nude mice. The inoculation position was 2 mm lateral and 2 mm posterior to the anterior fontanel. Tumor size was estimated from luciferase volume measurements and MRI. The mice were sacrificed when they exhibited disturbed activity or convulsion. The brain was then harvested and embedded in paraffin.
Response Summary	YTHDF2 accelerated UBXN1 mRNA degradation via METTL3-mediated m6A, which, in turn, promoted Nuclear factor NF-kappa-B p105 subunit (NF-Kappa-B/NFKB1) activation. YTHDF2 promotes the malignant progression of gliomas and revealed important insight into the upstream regulatory mechanism of NF-Kappa-B activation via UBXN1 with a primary focus on m6A modification.

POU domain, class 5, transcription factor 1 (POU5F1)

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				[98]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Pathway Response	RNA degradation			hsa03018
Cell Process	Cancer metastasis
In-vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
Response Summary	YTHDF2 promotes the CSC liver phenotype and cancer metastasis by modulating the m6A methylation of POU domain, class 5, transcription factor 1 (POU5F1) mRNA. YTHDF2 expression is positively correlated with OCT4 expression and m6A levels in the 5'-UTR of OCT4 mRNA in clinical hepatocellular carcinoma specimens.

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

Target Gene

Insulin resistance [ICD-11: 5A44]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[99]
Responsed Disease	Insulin resistance [ICD-11: 5A44]
Responsed Drug	Arsenite		Phase 2	Drug Info
In-vitro Model	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926

Programmed cell death 1 (PD-1)

Target Gene

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				[3]
Responsed Disease	Melanoma [ICD-11: 2C30]
Responsed Drug	PMID31239444-anti-PD1 antibody		Investigative	Drug Info
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	mRNA decay
In-vitro Model	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
	CHL-1	Melanoma	Homo sapiens	CVCL_1122
	624-mel	Melanoma	Homo sapiens	CVCL_8054
	NHEM (Normal Human Epidermal Melanocytes)
	SK-MEL-30	Cutaneous melanoma	Homo sapiens	CVCL_0039
	WM115	Melanoma	Homo sapiens	CVCL_0040
	WM35	Melanoma	Homo sapiens	CVCL_0580
	WM3670	Melanoma	Homo sapiens	CVCL_6799
	WM793	Melanoma	Homo sapiens	CVCL_8787
In-vivo Model	When the tumors reached a volume of 80-100 mm³, mice were treated with anti-PD-1 or isotype control antibody (200 ug/mouse) by i.p. injection, every other day for three times. For IFNγ blockade treatment, C57BL/6 mice were treated with anti-IFNγ antibody or isotype control IgG (250 ug/mouse) every other day after tumor cell inoculation.
Response Summary	These findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade reduces the resistance to immunotherapy in melanoma. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including Programmed cell death 1 (PD-1) (PDCD1), CXCR4, and SOX10, leading to increased RNA decay through the m6A reader YTHDF2.

Proliferation-associated protein 2G4 (PA2G4)

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				[100]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Cell Process	Cell metastatic
In-vitro Model	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	HLF	Adult hepatocellular carcinoma	Homo sapiens	CVCL_2947
	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	For lung metastasis model, 1 × 10⁶ HCC cells suspended in 100 ul serum free DMEM were injected via the tail vein of nude mice.
Response Summary	Proliferation-associated protein 2G4 (PA2G4) plays a pro-metastatic role by increasing FYN expression through binding with YTHDF2 in HCC. PA2G4 becomes a reliable prognostic marker or therapeutic target for HCC patients.

Pyruvate kinase PKM (PKM2/PKM)

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		[75]
Responsed Disease	Liver hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Down regulation
In-vivo Model	Male BALB/c nude mice (aged 4-6 weeks; n = 5/group) were obtained from Vital River Laboratory Animal Technology (Beijing, China). MHCC97H or Huh7 cells (2 × 10⁶ cells/mouse) stably transfected with lentivirus containing different plasmids in 100 μL DMEM were subcutaneously or orthotopically implanted into the nude mice.

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

Target Gene

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[5]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Up regulation
Pathway Response	Oxidative phosphorylation			hsa00190
In-vitro Model	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	RWPE-1	Normal	Homo sapiens	CVCL_3791
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
Response Summary	Knock-down of YTHDF2 or METTL3 significantly induced the expression of LHPP and NKX3-1 at both mRNA and protein level with inhibited phosphorylated RAC-alpha serine/threonine-protein kinase (AKT1). YTHDF2 mediates the mRNA degradation of the tumor suppressors LHPP and NKX3-1 in m6A-dependent way to regulate AKT phosphorylation-induced tumor progression in prostate cancer.

RB1-inducible coiled-coil protein 1 (RB1CC1/FIP200)

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		[49]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]

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

Target Gene

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[101]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Responsed Drug	Bacillus Calmette		Investigative	Drug Info
Target Regulation	Down regulation
In-vitro Model	MGH-U3	Bladder carcinoma	Homo sapiens	CVCL_9827
	SW780	Bladder carcinoma	Homo sapiens	CVCL_1728
	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
In-vivo Model	For xenograft studies, female mice between 4 and 6 weeks of age were used. Monoclonal cell lines showing a nearly complete absence of Ythdf2 and Ddx58 were used for in vivo experimentation. Mice were implanted with 2 × 10⁶ MGHU3 cells resuspended in 100 μL of Matrigel Matrix High Concentration (354248) and PBS mixture subcutaneously into the right flanks. Subcutaneous tumor growth was measured weekly by calipers, and the volume was calculated using the formula: volume = (length × width2)/2.

Serine/threonine-protein kinase mTOR (MTOR)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 6 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Asparagine inhibitor		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Chloroquine		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 3 Reporting the m6A-centered Disease Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Meclofenamate sodium		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 4 Reporting the m6A-centered Disease Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Rapamycin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 5 Reporting the m6A-centered Disease Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	CB-839		Phase 2	Drug Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition.
Experiment 6 Reporting the m6A-centered Disease Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	GLS-IN-968		Investigative	Drug Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition.

Serine/threonine-protein kinase PINK1, mitochondrial (PINK1)

Target Gene

Chronic kidney disease [ICD-11: GB61]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[102]
Responsed Disease	Diabetic nephropathy [ICD-11: GB61.Z]
Target Regulation	Down regulation
In-vitro Model	HK-2 [Human kidney]	Normal	Homo sapiens	CVCL_0302
In-vivo Model	Five week old male C57bl/6 mice (20 ± 2 g) were divided into the DKD model group and the control group. The fasting blood glucose of all the mice was measured before the experiment, and was required to be less than 7 mmol/L. The mice in the DKD model group were fed with a high-fat and high-sugar diet for 8 weeks. Then, 1 day after restoring the high-fat and high-sugar diet, the mice in the DKD model group were fasted for 16 h and injected with STZ at 50 mg/kg per day for 5 days. The fasting blood glucose was measured 2 weeks after the last injection. If the fasting blood glucose was greater than 16 mmol/L, the medium-term diabetes model had been established successfully. Then, the rat urine was collected and the ratio of urinary albumin to urinary muscle intoxication (AIb/Cr) was measured. The AIb/Cr was greater than 30 mg/g, indicating a diagnosis of DKD. The mice in the control group received standard chow and were injected with the same amount of normal saline. Subsequently, all DKD mice were randomly divided into the sh-NC group and the sh-METTL3 group. After establishment of the DKD model, the lentiviruses carrying sh-NC or sh-METTL3 (MOI = 50) were injected into the caudal vein at a dose of 1 μg/g according to the weight of mice, once a week for 8 weeks.

Serum response factor (SRF)

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				[104]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Responsed Drug	Tislelizumab		Approved	Drug Info
In-vitro Model	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022

Signal transducer and activator of transcription 5A (STAT5A)

Target Gene

Multiple myeloma [ICD-11: 2A83]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[105]
Responsed Disease	Multiple myeloma [ICD-11: 2A83.1]
Target Regulation	Down regulation
Pathway Response	MAPK signaling pathway	hsa04010
Response Summary	The analyses of m6A-RIP-seq and RIP-PCR indicated that Signal transducer and activator of transcription 5A (STAT5A) was the downstream target of YTHDF2, which was binding to the m6A modification site of STAT5A to promote its mRNA degradation. ChIP-seq and PCR assays revealed that STAT5A suppressed multiple myelomacell proliferation by occupying the transcription site of MAP2K2 to decrease ERK phosphorylation.

Splicing factor 3A subunit 3 (SF3A3)

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		[106]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Cell Process	Immunity
Response Summary	YTHDF2 expression was associated positively with Splicing factor 3A subunit 3 (SF3A3) expression, which implied that they cooperate in LIHC progression.

Stearoyl-CoA desaturase (SCD)

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				[107]
Responsed Disease	Colon cancer [ICD-11: 2B90]
In-vitro Model	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In-vitro Model	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547

Stimulator of interferon genes protein (STING1)

Target Gene

Picornavirus infections presenting in the skin or mucous membranes [ICD-11: 1F05]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[109]
Responsed Disease	Picornavirus infections presenting in the skin or mucous membranes [ICD-11: 1F05.3]

Thioredoxin domain-containing protein 5 (TXNDC5)

Target Gene

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[111]
Responsed Disease	Cervical cancer [ICD-11: 2C77]

Transcription factor E2F3 (E2F3)

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		[112]
Responsed Disease	Liver cancer [ICD-11: 2C12]
Target Regulation	Down regulation

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

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[82]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	Immunity
In-vitro Model	CT26	Mouse colon adenocarcinoma	Mus musculus	CVCL_7254
	B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
In-vivo Model	2 × 10⁶ CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Response Summary	In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Transcription factor ISGF-3 components p91/p84 (Stat1) and Irf1 mRNA via Ythdf2.

Transcription factor SOX-10 (SOX10)

Target Gene

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				[3]
Responsed Disease	Melanoma [ICD-11: 2C30]
Responsed Drug	PMID31239444-anti-PD1 antibody		Investigative	Drug Info
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	mRNA decay
In-vitro Model	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
	CHL-1	Melanoma	Homo sapiens	CVCL_1122
	624-mel	Melanoma	Homo sapiens	CVCL_8054
	NHEM (Normal Human Epidermal Melanocytes)
	SK-MEL-30	Cutaneous melanoma	Homo sapiens	CVCL_0039
	WM115	Melanoma	Homo sapiens	CVCL_0040
	WM35	Melanoma	Homo sapiens	CVCL_0580
	WM3670	Melanoma	Homo sapiens	CVCL_6799
	WM793	Melanoma	Homo sapiens	CVCL_8787
In-vivo Model	When the tumors reached a volume of 80-100 mm³, mice were treated with anti-PD-1 or isotype control antibody (200 ug/mouse) by i.p. injection, every other day for three times. For IFNγ blockade treatment, C57BL/6 mice were treated with anti-IFNγ antibody or isotype control IgG (250 ug/mouse) every other day after tumor cell inoculation.
Response Summary	These findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade reduces the resistance to immunotherapy in melanoma. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and Transcription factor SOX-10 (SOX10), leading to increased RNA decay through the m6A reader YTHDF2.

Transcription factor SOX-2 (SOX2)

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				[85]
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulation	Down regulation
In-vitro Model	MRC-9	Normal	Homo sapiens	CVCL_2629
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1703	Lung squamous cell carcinoma	Homo sapiens	CVCL_1490
	H1795 (Lung cancer H1795 cell lines were purchased from ATCC, USA)
	NCI-H1792	Lung adenocarcinoma	Homo sapiens	CVCL_1495
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428

Transforming growth factor beta-1 proprotein (TGFB1)

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	Lung cancer [ICD-11: 2C25]
Target Regulation	Down regulation
Pathway Response	mRNA surveillance pathway			hsa03015
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Response Summary	YTHDF2 inhibits the migration and invasion of lung adenocarcinoma cells by regulating the FAM83D-Transforming growth factor beta-1 proprotein (TGFB1)-pSMAD2/3 pathway, which will play an important role in lung cancer metastasis.

Tyrosine-protein kinase Fyn (FYN)

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				[100]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Cell Process	Cell metastatic
In-vitro Model	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	HLF	Adult hepatocellular carcinoma	Homo sapiens	CVCL_2947
	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	For lung metastasis model, 1 × 10⁶ HCC cells suspended in 100 ul serum free DMEM were injected via the tail vein of nude mice.
Response Summary	PA2G4 plays a pro-metastatic role by increasing Tyrosine-protein kinase Fyn (FYN) expression through binding with YTHDF2 in HCC. PA2G4 becomes a reliable prognostic marker or therapeutic target for HCC patients.

Ubiquitin carboxyl-terminal hydrolase 4 (USP4)

Target Gene

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[71]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Target Regulation	Down regulation
In-vitro Model	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
In-vivo Model	A total of 1 × 10⁶ PC3 cells or DU145 cells suspended in a mixture of 100 uL PBS and Matrigel were subcutaneously injected into BALB/c nude mice. Tumor weight were measured 2 months after the engraftment. To evaluate the role of METTL3 in tumor metastasis, PC3 cells with or without knockdown of METTL3 were injected into SCID mice through the tail vein (1 × 10⁶ cells per mouse). After eight weeks, mice were sacrificed and their lung tissues were collected for subsequent analyses.
Response Summary	m6A modification levels were markedly upregulated in human PCa tissues due to increased expression of METTL3. METTL3 mediates m6A modification of Ubiquitin carboxyl-terminal hydrolase 4 (USP4) mRNA at A2696, and m6A reader protein YTHDF2 binds to and induces degradation of USP4 mRNA by recruiting RNA-binding protein HNRNPD to the mRNA. Decrease of USP4 fails to remove the ubiquitin group from ELAVL1 protein, resulting in a reduction of ELAVL1 protein. Lastly, downregulation of ELAVL1 in turn increases ARHGDIA expression, promoting migration and invasion of PCa cells.

Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)

Target Gene

Obesity [ICD-11: 5B81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[37]
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagy
	Adipogenesis regulation
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
	Pig primary preadipocytes (Isolated from cervical subcutaneous adipose tissue of piglets)
In-vivo Model	Mice were maintained at 22 ± 2 ℃ with a humidity of 35 ± 5% under a 12 h light and 12 h dark cycle, with free access to water and food. For the HFD experiment, female control (Fto^flox/flox) and adipose-selective fto knockout (Fabp4-Cre Fto^flox/flox, fto-AKO) mice were fed with high-fat diet (60% fat in calories; Research Diets, D12492) for the desired periods of time, and food intake and body weight were measured every week after weaning (at 3 weeks of age).
Response Summary	Atg5 and Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) were the targets of YTHDF2 (YTH N6-methyladenosine RNA binding protein 2). Upon FTO silencing, Atg5 and Atg7 transcripts with higher m6A levels were captured by YTHDF2, which resulted in mRNA degradation and reduction of protein expression, thus alleviating autophagy and adipogenesis.

Osteoarthritis [ICD-11: FA05]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[47]
Responsed Disease	Osteoarthritis [ICD-11: FA05]

UBX domain-containing protein 1 (UBXN1)

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				[96]
Responsed Disease	Glioma [ICD-11: 2A00.0]
Target Regulation	Down regulation
Pathway Response	NF-kappa B signaling pathway			hsa04064
In-vitro Model	U87 (A primary glioblastoma cell line)
	N33 (The GBM patient-derived cell line)
	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
	H4	Astrocytoma	Homo sapiens	CVCL_1239
In-vivo Model	Five-week-old female BALB/c nude mice (Charles Rivers, Beijing, China) were selected for the experiments. U87 cells (5 × 10⁵) transfected with an empty vector, YTHDF2 overexpression, or METTL3 overexpression vectors were suspended in PBS and injected into the right frontal node of nude mice. The inoculation position was 2 mm lateral and 2 mm posterior to the anterior fontanel. Tumor size was estimated from luciferase volume measurements and MRI. The mice were sacrificed when they exhibited disturbed activity or convulsion. The brain was then harvested and embedded in paraffin.
Response Summary	YTHDF2 accelerated UBX domain-containing protein 1 (UBXN1) mRNA degradation via METTL3-mediated m6A, which, in turn, promoted NF-Kappa-B activation. YTHDF2 promotes the malignant progression of gliomas and revealed important insight into the upstream regulatory mechanism of NF-Kappa-B activation via UBXN1 with a primary focus on m6A modification.

Growth arrest specific 5 (GAS5)

Target Gene

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[115]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulation	Up regulation
Cell Process	Cell proliferation and metastasis
In-vitro Model	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	Normal cervical epithelium cell line (HCvEpC) (Isolated from cervical tissue)
In-vivo Model	200 uL PBS containing 1×10⁷ cells of stable cells were subcutaneously injected into male BALB/c athymic nude mice (6-week old, 18-20 g).
Response Summary	The GAS5-AS1 expression in cervical cancer tissues was markedly decreased when compared with that in the adjacent normal tissues. GAS5-AS1 interacted with the tumor suppressor Growth arrest specific 5 (GAS5), and increased its stability by interacting with RNA demethylase ALKBH5 and decreasing GAS5 N6-methyladenosine (m6A) modification. m6A-mediated GAS5 RNA degradation relied on the m6A reader protein YTHDF2-dependent pathway.

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

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[116]
Responsed Disease	Vascular disorders of the liver [ICD-11: DB98.8]
Target Regulation	Down regulation
In-vivo Model	The in vivo assay was approved by the Animal Care and Use Committee of Anhui Medical University. And all experimental procedures and animal care were in accordance with the institutional ethics guidelines for animal experiments. The C57BL/6 mice (male, 8-10 weeks old) were housed (six per cage) in a specific and opportunistic pathogen-free facility and maintained on a 12-hlight-dark cycle with casually access to food and water. Detailed descriptions of the cell culture, cardiac fibrosis model, and treatment with lentiviral, were given in the Supplementary methods online.

LINC00902 (TUSC7)

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				[117]
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Responsed Drug	Erlotinib		Approved	Drug Info
Target Regulation	Down regulation
Pathway Response	Notch signaling pathway			hsa04330), EGFR tyrosine kinase inhibitor resistance
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
In-vivo Model	Control vector, TUSC7 knockout, FLI-06 treated H1975 cells (1*10⁷) cells were suspended in 100 uL of serum-free DMEM medium (Hyclone, USA), mixed with matrix gel (Corning, USA), and then were injected subcutaneously. The changes in the tumor size were recorded every 3 or 5 days.
Response Summary	In lung adenocarcinoma, The miR-146a/Notch signaling was sustained highly activated in a m6A dependent manner, and the m6A regulator of YTHDF2 suppressed LINC00902 (TUSC7), both of which contributed to the resistant features. Functionally, the sponge type of TUSC7 regulation of miR-146a inhibited Notch signaling functions, and affected the cancer progression and stem cells' renewal in Erlotinib resistant PC9 cells (PC9ER) and Erlotinib resistant HCC827 cells (HCC827ER) cells.

Long intergenic non-protein coding RNA 1273 (LINC01273)

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				[118]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Sorafenib		Approved	Drug Info
Target Regulation	Down regulation
In-vitro Model	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
Response Summary	Long intergenic non-protein coding RNA 1273 (LINC01273) was modified with m6A, METTL3 increased LINC01273 m6A modification, followed by LINC01273 decay in the presence of YTHDF2, a m6A 'reader'. And LINC01273 plays a key role in sorafenib resistant HCC cells.

Long intergenic non-protein coding RNA 470 (LINC00470)

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				[87]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Pathway Response	Gastric cancer			hsa05226
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
In-vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	GES-1	Normal	Homo sapiens	CVCL_EQ22
	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
Response Summary	Long intergenic non-protein coding RNA 470 (LINC00470)-METTL3-mediated PTEN mRNA degradation relied on the m6A reader protein YTHDF2-dependent pathway. LINC00470 served as a therapeutic target for Gastric cancer patients.

Nuclear paraspeckle assembly transcript 1 (NEAT1)

Target Gene

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				[119]
Responsed Disease	Renal cell carcinoma [ICD-11: 2C90]
Target Regulation	Down regulation
Cell Process	Cell proliferation and metastasis
In-vitro Model	769-P	Renal cell carcinoma	Homo sapiens	CVCL_1050
	786-O	Renal cell carcinoma	Homo sapiens	CVCL_1051
	HK2	Normal	Acipenser baerii	CVCL_YE28
In-vivo Model	Mouse subcutaneous xenograft and lung metastasis experiments were carried out with six 4-week-old male BALB/c nude mice.
Response Summary	In renal cell carcinoma, YTHDF2 accelerated the degradation of Nuclear paraspeckle assembly transcript 1 (NEAT1)_1 by selectively recognizing METTL14-mediated m6A marks on Nuclear paraspeckle assembly transcript 1 (NEAT1)_1.

X inactive specific transcript (XIST)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[120]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
Cell Process	Tumorigenicity and metastasis
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	NCM460	Normal	Homo sapiens	CVCL_0460
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In-vivo Model	For liver metastasis model, mice were anaesthetized and an incision was made through the skin and peritoneum to expose the spleen. 1 × 10⁶ HCT116 cells were injected into the spleen (n = 4 each group).
Response Summary	In colorectal cancer, knockdown of METTL14 substantially abolished m6A level of X inactive specific transcript (XIST) and augmented XIST expression. m6A-methylated XIST was recognized by YTHDF2, a m6A reader protein, to mediate the degradation of XIST.

microRNA 126 (MIR126)

Target Gene

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[121]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Up regulation
In-vitro Model	Mono-Mac-6	Adult acute monocytic leukemia	Homo sapiens	CVCL_1426
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Cells were collected from the CD45.2 Ythdf2fl/flMx1-Cre mice, enriched for lin-population, and transduced with retroviral MA9 alone or retroviral MA9 + MSCV-pre-miR-126/MSCV-pre-miR-Control by spinoculation as described before. Clonal cells from CFA assays were washed and suspended together with healthy mouse BM cells (0.5 million CFA cells + 1 million healthy BM per mouse) with ice-cold PBS, and subsequently injected via the tail vein into lethally (900 rads) irradiated 8 to 10-week-old B6.SJL (CD45.1) recipient mice. Ten days after the injection, knockout was induced by i.p. delivering of poly I:C (428750 R&D Systems) at 300 μg each time per mice every other day for five times. Mice were observed regularly after cell injection and samples were collected at the end point.

microRNA 145 (MIR145)

Target Gene

Epilepsy due to structural or metabolic conditions or diseases [ICD-11: 8A60]

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	Epilepsy due to structural or metabolic conditions or diseases [ICD-11: 8A60.5]

hsa-mir-181b-1

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				[20]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Down 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 YAP expression through dual mechanisms with direct m6A methylation of YAP and indirect downregulation of YAP level due to methylation of hsa-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.

hsa-miR-1915-3p

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[6]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulation	Down regulation
Pathway Response	TNF signaling pathway			hsa04668
Cell Process	Cell migration
	Cell invasion
	Epithelial-mesenchymal transition
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Response Summary	hsa-miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor KLF4. miR-1915-3p function as a tumor suppressor by targeting SET and has an anti-metastatic therapeutic potential for lung cancer treatment.

5-hydroxytryptamine receptor 3A (HTR3A)

Target Gene

Pain disorders [ICD-11: 8E43]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[122]
Responsed Disease	Neuropathic pain [ICD-11: 8E43.0]
Target Regulation	Down regulation

Alpha-synuclein (SNCA)

Target Gene

Parkinson disease [ICD-11: 8A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[123]
Responsed Disease	Parkinson disease [ICD-11: 8A00]
Target Regulation	Up regulation
In-vitro Model	SN4741	N.A.	Mus musculus	CVCL_S466
In-vivo Model	Male nude mice (6 weeks old) were purchased from the Shanghai Laboratory Animal Central (Shanghai, China). 95D cells (1 × 10⁷) transfected with sh-HNRNPA2B1 or sh-NC lentiviruses were injected subcutaneously into the right flanks of mice. After 8 weeks, the mice were sacrificed, and the xenografted tumors were collected for hematoxylin-eosin (HE) staining and IHC analysis.

Apoptosis regulatory protein Siva (SIVA1)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[124]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Responsed Drug	Fluorouracil		Approved	Drug Info
Target Regulation	Down regulation
In-vitro Model	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HEK293T	Normal	Homo sapiens	CVCL_0063
	MC-38	Mouse colon adenocarcinoma	Mus musculus	CVCL_B288
In-vivo Model	For the tumor metastasis mouse model, 5-week-old C57BL/6 mice were randomly grouped and injected with 5 × 10⁵ Control or shFTO stable MC38 cells via tail vein. Drug administration was adopted after 48 h. Drug administration (intraperitoneally): DMSO, 5-FU (50 mg/kg every 2 days) or Rhein (10 mg/kg every 2 days). To detect lung metastasis, mice were killed 2 weeks after tumor cell injection. Lung tissues were harvested and fixed with 4% PFA for paraffin-embedded section and lung metastases were detected with Nikon microscopy. For tumor intraperitoneal mouse model, 2 × 10⁶ Dox-shCtrl, Dox-shFTO stable HCT8/5-FU cells were injected into 5-week-old male BALB/C nude mice. Drug administration was adopted after 48 h. Drug administration (intraperitoneally): DMSO, 5-FU (50 mg/kg every 2 days) or FB23-2 (10 mg/kg every 2 days). For tumor intraperitoneal mouse model, 5 × 10⁵ shCtrl, shFTO-1, shFTO-2 stable MC38 cells were injected into 5-week-old C57BL/6 mice. Drug administration was adopted after 48 h. Drug administration (intraperitoneally): DMSO, 5-FU (50 mg/kg every 2 days) or Rhein (10 mg/kg every 2 days).

Aryl hydrocarbon receptor (AHR)

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				[104]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
Responsed Drug	Tislelizumab		Approved	Drug Info
In-vitro Model	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022

Carbohydrate sulfotransferase 11 (CHST11)

Target Gene

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

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[125]
Responsed Disease	Diffuse large B-cell lymphomas [ICD-11: 2A81]
Target Regulation	Down regulation
In-vitro Model	OCI-Ly1	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_1879
	OCI-Ly8	Diffuse large B-cell lymphoma germinal center B-cell type	Homo sapiens	CVCL_8803
	OCI-Ly3	Diffuse large B-cell lymphoma activated B-cell type	Homo sapiens	CVCL_8800
	VAL	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_1819
	U-2932	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_1896
In-vivo Model	A total of 1 × 10⁷ KIAA1429 stable knockdown OCI-LY1 cells or CHST11 stable knockdown OCI-LY1 cells were injected subcutaneously into the right armpit of mice. Two investigators who were blinded to the mice allocation observed the general condition of mice and tumor growth every 2 days, measuring tumor size with a vernier caliper upon the tumor size was higher than the skin surface and recording it.

Cardiac mesoderm enhancer-associated non-coding RNA (CARMN)

Target Gene

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[126]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulation	Down regulation
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
In-vivo Model	After approval by Ethics Committee of School of Public Health, Southeast University, BALB/c nude mice (4-5 weeks old) were purchased and raised in SPF animal house. 1 × 10⁷ HeLa cells or NC cells with stable overexpression of CARMN were prepared in each nude mouse. The mice were killed 3 weeks later, and tumor volume was measured.

Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A)

Target Gene

Heart failure [ICD-11: BD1Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[127]
Responsed Disease	Heart failure [ICD-11: BD1Z]
Target Regulation	Down regulation

CBSLR

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				[64]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Proteasome pathway degradation
In-vitro Model	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
	MKN45	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
	MKN28	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_1416
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	GSE-1 (Gse-1 is a human gastric epithelial cell line)
	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
Response Summary	CBSLR interacted with YTHDF2 to form a CBSLR/YTHDF2/CBS signaling axis that decreased the stability of CBS mRNA by enhancing the binding of YTHDF2 with the m6A-modified coding sequence (CDS) of CBS mRNA. Reveal a novel mechanism in how HIF1-Alpha/CBSLR modulates ferroptosis/chemoresistance in GC, illuminating potential therapeutic targets for refractory hypoxic tumors.

CD40 ligand (CD40L)

Target Gene

Immune-related diseases [ICD-11: 4B4Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[128]
Responsed Disease	Immune-related diseases [ICD-11: 4B4Z]
Target Regulation	Down regulation

CD70 antigen (CD70)

Target Gene

Thyroid Cancer [ICD-11: 2D10]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[129]
Responsed Disease	Papillary thyroid cancer [ICD-11: 2D10.1]
Responsed Drug	JNJ-74494550		Phase 2	Drug Info
Target Regulation	Down regulation
In-vitro Model	Nthy-ori 3-1	Normal	Homo sapiens	CVCL_2659
	B-CPAP	Thyroid gland carcinoma	Homo sapiens	CVCL_0153
	K1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_2537
	C-643	Thyroid gland anaplastic carcinoma	Homo sapiens	CVCL_5969
	BHT-101	Thyroid gland anaplastic carcinoma	Homo sapiens	CVCL_1085
	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
In-vivo Model	NCG mice (female, 4-5 weeks old, purchased from Jiangsu GemPharmatech) were acclimated for 1 week and were selected randomly to subcutaneously (s.c.) injected with 100 μl suspensions of 1 × 10⁶ thyroid cancer cell lines. All mice were housed in animal facility under specific pathogen-free conditions. After 7 day, 5 × 10⁶ huPBMCs were intravenously (i.v.) inoculated into mice. Mice were treated intravenously with anti-PD-1 mAb (nivolumab, 200 μg per injection), Combination (nivolumab + anti-CD70 mAb cusatuzumab, 200 μg per injection each), or PBS once a week. The treatment with M2-TAMs EVs or PBS continued in mice at 2ug EVs per injection at the tumor site twice a week [24]. The body weight of mice and the length (mm) and width (mm) of tumors were monitored every 3 or 4 days. Tumor volume (mm3) was calculated as Length × Width2 × 1/2. Tumor growth analyses were limited to 3 to 4 weeks because following this period mice started to show signs of xenograft-versus-host disease (xGVHD). Therefore, after 14 days or 21 days of PBMCs implantation, the mice were euthanized.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[129]
Responsed Disease	Papillary thyroid cancer [ICD-11: 2D10.1]
Target Regulation	Down regulation
In-vitro Model	Nthy-ori 3-1	Normal	Homo sapiens	CVCL_2659
	B-CPAP	Thyroid gland carcinoma	Homo sapiens	CVCL_0153
	K1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_2537
	C-643	Thyroid gland anaplastic carcinoma	Homo sapiens	CVCL_5969
	BHT-101	Thyroid gland anaplastic carcinoma	Homo sapiens	CVCL_1085
	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
In-vivo Model	NCG mice (female, 4-5 weeks old, purchased from Jiangsu GemPharmatech) were acclimated for 1 week and were selected randomly to subcutaneously (s.c.) injected with 100 μl suspensions of 1 × 10⁶ thyroid cancer cell lines. All mice were housed in animal facility under specific pathogen-free conditions. After 7 day, 5 × 10⁶ huPBMCs were intravenously (i.v.) inoculated into mice. Mice were treated intravenously with anti-PD-1 mAb (nivolumab, 200 μg per injection), Combination (nivolumab + anti-CD70 mAb cusatuzumab, 200 μg per injection each), or PBS once a week. The treatment with M2-TAMs EVs or PBS continued in mice at 2ug EVs per injection at the tumor site twice a week [24]. The body weight of mice and the length (mm) and width (mm) of tumors were monitored every 3 or 4 days. Tumor volume (mm3) was calculated as Length × Width2 × 1/2. Tumor growth analyses were limited to 3 to 4 weeks because following this period mice started to show signs of xenograft-versus-host disease (xGVHD). Therefore, after 14 days or 21 days of PBMCs implantation, the mice were euthanized.

Circ_AFF2

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[130]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
In-vitro Model	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	HT-29	Colon adenocarcinoma	Homo sapiens	CVCL_0320
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	NCM460	Normal	Homo sapiens	CVCL_0460

Circ_ASK1

Target Gene

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[131]
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
Responsed Drug	Gefitinib		Approved	Drug Info
Target Regulation	Down regulation
Cell Process	Cell apoptosis
In-vitro Model	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
	SK-LU-1	Lung adenocarcinoma	Homo sapiens	CVCL_0629
	NCI-H1993	Lung adenocarcinoma	Homo sapiens	CVCL_1512
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	16HBE14o-	Normal	Homo sapiens	CVCL_0112
In-vivo Model	Established a xenograft model in BALB/c nude mice by inoculating HCC827-GR cells transfected with the constructs for circASK1 silencing, ASK1-272a.a overexpression and ASK1-272a.a overexpression/circASK1 knockdown.
Response Summary	Increased YTHDF2-mediated endoribonucleolytic cleavage of m6A-modified Circ_ASK1 accounts for its downregulation in gefitinib-resistant cells. Either METTL3 silencing or YTHDF2 silencing suppressed the decay of circASK1 in HCC827-GR cells. This study provides a novel therapeutic target to overcome gefitinib resistance in LUAD patients.

Circ_FUT8

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				[132]
Responsed Disease	Lung adenocarcinoma [ICD-11: 2C25.0]
In-vitro Model	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
In-vivo Model	Thirty female BALB/c nude mice weighing 18-22 g were randomly assigned to six groups. PC9-Mock, PC9-circFUT8, A549-sh-scramble, and A549-sh-circFUT8 cells were prepared as a suspension of 4 × 10⁵ cells in 200 μL saline, respectively, and injected into the tail vein. Mice were sacrificed at 6 weeks post injection and examined microscopically by hematoxylin and eosin (H&E) staining for the development of lung metastases.

Circ_GPATCH2L

Target Gene

Spinal pain [ICD-11: ME84]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[133]
Responsed Disease	Spinal pain [ICD-11: ME84.2]

Circ_IRF2

Target Gene

Hepatic fibrosis/cirrhosis [ICD-11: DB93]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[134]
Responsed Disease	Hepatic fibrosis/cirrhosis [ICD-11: DB93]
Target Regulation	Down regulation
In-vitro Model	LX-2	N.A.	Homo sapiens	CVCL_5792
In-vivo Model	For the TAA (Sigma-Aldrich, USA) induced mouse liver fibrosis model, briefly, TAA (200 mg/kg, diluted in saline) was injected 3 times weekly for 8 weeks. Mice were sacrificed 24 h after the last administration.

Circ_RERE

Target Gene

Osteoarthritis [ICD-11: FA05]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[135]
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Responsed Drug	ICG-001	Investigative	Drug Info
Target Regulation	Down regulation

Circ_RNF13

Target Gene

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[136]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulation	Down regulation
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	C-4-I	Cervical squamous cell carcinoma	Homo sapiens	CVCL_2253
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
In-vivo Model	Stably transfected cell lines were created by silencing circRNF13 in CC SiHa cells. Once xenografts were established, the tumors reached an approximate volume of 200 mm3. A single dose of 15 Gy irradiation was administered to female BALB/c nude mice (4-5 weeks old) in the murine model. The tumor volume was measured and recorded using vernier calipers every five days after irradiation. After 30 days, the mice were euthanized under anesthesia, and tumor tissue was collected for further investigations.

Circ_SLC9A6

Target Gene

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

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[137]
Responsed Disease	Nonalcoholic fatty liver disease [ICD-11: DB92.Z]
Target Regulation	Down regulation

Complement C1q subcomponent subunit A (C1QA)

Target Gene

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

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[138]
Responsed Disease	Diffuse large B-cell lymphomas [ICD-11: 2A81]
Responsed Drug	Rituximab	Approved	Drug Info
Target Regulation	Down regulation
In-vivo Model	Approximately 2 × 10⁶ Farage/R or Farage/S cells stably transfected with shNC, shC1qA or shMETTL3 were subcutaneously injected into the left flank of each mouse. When the tumor volume reached ~100 mm3, each mouse received an intraperitoneal injection of Rituximab (20 mg/kg) every 4 days for a total of 5 injections. The diameter of each tumor was examined every 4 days using a caliper, and tumor volume was calculated as follows: (length × width2)/2. At 28 days after xenograft, the mice were sacrificed and the tumors were weighed and collected.

Cysteine methyltransferase DNMT3A (DNMT3A)

Target Gene

Chronic obstructive pulmonary disease [ICD-11: CA22]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[140]
Responsed Disease	Chronic obstructive pulmonary disease [ICD-11: CA22]
Target Regulation	Down regulation
In-vivo Model	Male BALB/c mice (SJA Laboratory Animal Company, Hunan, China) with age of 6-8 weeks were used in this study to establish COPD model. Mice were housed in individually ventilated cages under a pathogen-free condition, with ad libitum access to food and water. Animal welfare was monitored daily, and all efforts were made to minimize suffering. All animal procedures were conducted in accordance with the guidelines for use of laboratory animals, with approval from the Institutional Animal Care and Use Committee at Jiangxi Provincial People's Hospital (The First Affiliated Hospital of Nanchang Medical College).

Cysteine protease ATG4A (ATG4A)

Target Gene

Intervertebral disc degeneration [ICD-11: FA80]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[141]
Responsed Disease	Intervertebral disc degeneration [ICD-11: FA80]
Target Regulation	Down regulation

D26496

Target Gene

Injury of nerves at hip or thigh level [ICD-11: NC74]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[142]
Responsed Disease	Injury of nerves at hip or thigh level [ICD-11: NC74.0]
Target Regulation	Down regulation
In-vitro Model	Schwann cells (A type of glial cell that surrounds neurons)
In-vivo Model	Rats were randomly divided into 4 groups: sham group (6 rats), SNI model group (24 rats), SNI + vector group (6 rats), and SNI + pcDNA-D26496 group (6 rats). D26496 overexpressed Adeno associated virus (AAVs, virus titer: 1.88E + 13) and vector (OBiO Technology Corp., Shanghai, China) were injected into the epineurium of sciatic nerve of rats (5 μL for each) in the SNI + vector group and SNI + pcDNA-D26496 group, respectively.

DNA replication licensing factor MCM7 (MCM2)

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				[69]
Responsed Disease	Liver hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	OSMI-1		Investigative	Drug Info
Target Regulation	Up regulation
In-vitro Model	HepAD38	Hepatoblastoma	Homo sapiens	CVCL_M177
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	HEK293	Normal	Homo sapiens	CVCL_0045
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	For the xenograft implantation model, 2 × 10⁶ MHCC-97H cells were subcutaneously injected into the flank of nude mice.

Dual specificity protein phosphatase 1 (DUSP1)

Target Gene

Bacterial infection [ICD-11: 1C41]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[143]
Responsed Disease	Bacterial infection [ICD-11: 1C41]
Target Regulation	Down regulation
In-vitro Model	RAW 264.7	Mouse leukemia	Mus musculus	CVCL_0493

E3 ubiquitin-protein ligase pellino homolog 2 (PELI2)

Target Gene

Unspecific body region injury [ICD-11: ND56]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[144]
Responsed Disease	Cutaneous wound [ICD-11: ND56.0]
Target Regulation	Down regulation
In-vitro Model	HaCaT	Normal	Homo sapiens	CVCL_0038

Elongation factor 2 (EEF2)

Target Gene

Heart failure [ICD-11: BD1Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[145]
Responsed Disease	Heart failure [ICD-11: BD1Z]
In-vivo Model	All experiments were performed in 10-wk-old male mice unless otherwise indicated. Mice carrying a floxed Ythdf2 allele [24] and the alpha-MHC Cre Ribo-tag mouse [21] were crossed to obtain a cardiomyocyte specific Ythdf2 KO mouse expressing a HA-tagged RPL22. The mice were housed in a temperature- and humidity-controlled facility with a 12-h light-dark cycle. At 10 wk. of age, male mice underwent TAC (27 gauge needle) or sham operation, as previously described [25]. For echocardiography, the mice were anesthetized with 2% isoflurane and scanned using a Vevo2100 imaging system (Visual Sonics) as previously described [46]. Institutional Animal Care and Use Committee approval was obtained for all animal studies.

ETS translocation variant 5 (ETV5)

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		[146]
Responsed Disease	Liver cancer [ICD-11: 2C12]
Target Regulation	Up regulation

Fibulin-1 (FBLN1)

Target Gene

Maxillofacial bone defect is a critical obstacle for maxillofacial tumors and periodontal diseases. [ICD-11: NA02]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[147]
Responsed Disease	Maxillofacial bone defect is a critical obstacle for maxillofacial tumors and periodontal diseases. [ICD-11: NA02]
Target Regulation	Down regulation
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063

Glutamate--cysteine ligase regulatory subunit (GCLM)

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				[148]
Responsed Disease	Glioblastoma [ICD-11: 2A00.00]
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	ENSA (A human embryonic stem derived neural progenitor cell)
	NSC11 (Pluripotent derived neural progenitor cell)
In-vivo Model	Intracranial xenografts were generated by implanting 20,000 patient derived GSCs into the right cerebral cortex of mice at a depth of 3.5 mm. Housing conditions and animal status were supervised by a veterinarian. Euthanasia was taken until neurologic symptoms included hunched posture, gait changes, or lethargy were observed, at which point they were sacrificed. Brains were harvested and frozen at -80 °C with O.C.T. compound (4583, Tissue-Tek) directly or fixed in 4 % formaldehyde for 48 hours then stored in 70 % ethanol, and sectioned.

GTP-binding protein 4 (GTPBP4)

Target Gene

Picornavirus infections presenting in the skin or mucous membranes [ICD-11: 1F05]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[83]
Responsed Disease	Picornavirus infections presenting in the skin or mucous membranes [ICD-11: 1F05.3]
In-vitro Model	PK-15	N.A.	Sus scrofa	CVCL_2160
	HT-29	Colon adenocarcinoma	Homo sapiens	CVCL_0320
	IB-RS-2	N.A.	Sus scrofa	CVCL_4528
	CPTC-SVIL-1	N.A.	Oryctolagus cuniculus	CVCL_C2LN
	HEK293T	Normal	Homo sapiens	CVCL_0063
	BHK-21	N.A.	Mesocricetus auratus	CVCL_1914
	RD	Embryonal rhabdomyosarcoma	Homo sapiens	CVCL_1649

Heat shock 70 kDa protein 6 (HSPA6)

Target Gene

Endometrial cancer [ICD-11: 2C76]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[149]
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
In-vitro Model	Ishikawa	Endometrial adenocarcinoma	Homo sapiens	CVCL_2529
	HEK293	Normal	Homo sapiens	CVCL_0045
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030

Heme oxygenase 1 (HMOX1)

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				[150]
Responsed Disease	Pulmonary hypertension [ICD-11: BB01]
Target Regulation	Down regulation
In-vitro Model	MH-S	N.A.	Mus musculus	CVCL_3855

Diseases of the female genital system [ICD-11: GA6Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[151]
Responsed Disease	Diseases of the female genital system [ICD-11: GA6Z]
Target Regulation	Down regulation
In-vivo Model	Daily vaginal smears were collected between 4 and 6 PM, and rats showing four consecutive 4-day estrus cycles were chosen for constructing the endometrial injury model. Anesthesia was induced by injecting 3% mebumalnatrium (dose: 1.4 mL/kg) into the lumbar region, followed by a low midline abdominal incision for uterus exposure.

Histone acetyltransferase KAT2A (KAT2A)

Target Gene

Cardiomyopathy [ICD-11: BC43]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[152]
Responsed Disease	Diabetic cardiomyopathy [ICD-11: BC43.7]
Target Regulation	Up regulation

Insulin-like growth factor-binding protein 3 (IGFBP3)

Target Gene

Alzheimer disease [ICD-11: 8A20]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[49]
Responsed Disease	Alzheimer disease [ICD-11: 8A20]

Interleukin-6 receptor subunit alpha (IL6R)

Target Gene

Sepsis [ICD-11: 1G40]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[153]
Responsed Disease	Sepsis [ICD-11: 1G40]
Target Regulation	Down regulation
In-vitro Model	RAW 264.7	Mouse leukemia	Mus musculus	CVCL_0493

long intergenic non-protein coding RNA 115 (LINC00115)

Target Gene

Triple-negative breast cancer [ICD-11: 2C6Z]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[154]
Responsed Disease	Triple-negative breast cancer [ICD-11: 2C6Z]
Responsed Drug	Acetaminophen	Approved	Drug Info
Target Regulation	Down regulation

Lysine-specific demethylase 6B (KDM6B)

Target Gene

Inflammatory response [ICD-11: MG46]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[155]
Responsed Disease	Inflammatory response [ICD-11: MG46]
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006

Metalloproteinase inhibitor 4 (TIMP4)

Target Gene

Osteoarthritis [ICD-11: FA05]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[156]
Responsed Disease	Osteoarthritis [ICD-11: FA05]
Target Regulation	Up regulation
In-vivo Model	The male C57BL/6 mice (SPF, Eight-week-old) were randomly divided into four groups: sham (n = 6), model (n = 6), model + adeno-associated virus-negative control (AVV-shNC) (n = 6), and model + AVV-shWTAP groups (n = 6). After acclimating for one week, mice in other groups were treated with DMM surgery to induce OA as previously described except for the sham groups [19]. The mice in sham group were underwent only the skin of the right knee joint incision. The AAV-shNC and AAV-shWTAP were constructed by HANBIO (Shanghai, China). The AAV-shNC and AAV-shWTAP groups were intra-articularly injected with 10 μL of AAV-shNC and AAV-shWTAP (1 × 1015 vg/ml) through the medial parapatellar area at two weeks after the DMM operation, respectively.

Metalloreductase STEAP3 (STEAP3)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[157]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	RKO	Colon carcinoma	Homo sapiens	CVCL_0504
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	HT29	Colon cancer	Mus musculus	CVCL_A8EZ
	NCM460	Normal	Homo sapiens	CVCL_0460
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	Six to eight weeks old male BALB/c nu/nu mice were used. For orthotopic implantation, 1 × 10⁷ PBS suspended cells was injected subcutaneously. For the spleen injection model, 5 × 10⁵ cells were injected into the spleen through an incision on the left side of abdomen.

Mothers against decapentaplegic homolog 4 (SMAD4)

Target Gene

Hematological disorders [ICD-11: 3C0Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[43]
Responsed Disease	Hematological disorders [ICD-11: 3C0Z]
Target Regulation	Down regulation

Myocardial zonula adherens protein (MYZAP)

Target Gene

Cardiomyopathy [ICD-11: BC43]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[159]
Responsed Disease	Cardiomyopathy [ICD-11: BC43]
Target Regulation	Up regulation

Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1)

Target Gene

Spinal deformities [ICD-11: FA70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[160]
Responsed Disease	Spinal deformities [ICD-11: FA70.1]
Target Regulation	Down regulation
In-vitro Model	C2C12	Normal	Mus musculus	CVCL_0188

Paired box protein Pax-6 (PAX6)

Target Gene

Acute ischemic stroke [ICD-11: 8B11]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[161]
Responsed Disease	Acute ischemic stroke [ICD-11: 8B11]
In-vitro Model	BV-2	Normal	Mus musculus	CVCL_0182
In-vivo Model	C57BL/6 mice were anesthetized intraperitoneally with 1% sodium pentobarbital (100 mg/kg). The mouse was placed on a thermostatic blanket to maintain the rectal temperature at 37.0°C± 0.5°C during surgery. The left common carotid artery (CCA), external carotid artery (ECA), and internal carotid artery (ICA) were exposed through a midline incision in the cervico abdominal region. The CCA was ligated distally with surgical nylon monofilament.

Potassium channel subfamily K member 6 (KCNK6)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[163]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Up regulation

Prolyl endopeptidase FAP (FAP)

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				[164]
Responsed Disease	Non-small cell lung cancer [ICD-11: 2C25.Y]
Responsed Drug	VS-6063		Phase 2	Drug Info
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
In-vivo Model	The Laboratory Animal Center of Soochow University provided female BALB/c nude mice (5 weeks old). Mice were kept under specific pathogen-free conditions. They were injected intravenously (i.v.) with FTO-overexpressing and control A549 cells (1.8 × 10⁶ cells/mouse) to establish the in vivo model of NSCLC metastasis, and were then gavaged with dimethyl sulfoxide (DMSO) (25 mg/kg, daily) or the FAK inhibitor defactinib (VS6063) (Cat#S7654, Selleck, USA) (25 mg/kg, daily) beginning in the fifth week after injection. The mice were euthanized eight weeks after being inoculated, and their lungs were taken out and preserved in Bouin's solution for macroscopic investigation of metastatic nodules. Hematoxylin and eosin (H&E) staining of lung tissues was used to look for micrometastatic foci.

Protein flightless-1 homolog (FLII)

Target Gene

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[165]
Responsed Disease	Prostate adenocarcinoma [ICD-11: 2C82.0]
Target Regulation	Up regulation
In-vitro Model	RWPE-1	Normal	Homo sapiens	CVCL_3791
In-vivo Model	For tumor growth measurement, 5 × 10⁶ stably transfected 22RV1 cells were subcutaneously injected into mice at the flank site. Then, the volume (V) of xenograft tumors was examined once per week as follows: V = length × width2/2. After 4 weeks, the mice were euthanized via intraperitoneal injection of 150 mg/kg pentobarbital sodium, and the tumors were taken out and weighed, and collected for immunohistochemistry (IHC) to examine the expression of the proliferation marker Ki67 (1:200, ab16667, Abcam) in xenograft tumors. For tumor metastasis measurement, 5 × 10⁶ stably transfected 22RV1 cells were injected into mice through tail vein.

Protein NLRC5

Target Gene

Endometrial cancer [ICD-11: 2C76]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[166]
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulation	Up regulation

Protein wntless homolog (WLS)

Target Gene

Pain disorders [ICD-11: 8E43]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[167]
Responsed Disease	Neuropathic pain [ICD-11: 8E43.0]
Target Regulation	Down regulation
In-vitro Model	PC-12	Lung papillary adenocarcinoma	Homo sapiens	CVCL_S979
In-vivo Model	Rats were anesthetized with isoflurane (1.5%-2.5%), and a lateral thigh incision was made. The left sciatic nerve and its three peripheral branches were isolated after sciatic nerve resection. A 5-0 suture was used to ligate the common peroneal and tibial nerves. Then, distal transverse incisions were made at the ligation. All surgical procedures were completed within 20 min, with special care taken to avoid damaging the sural nerve. The rats in the sham group underwent the same sciatic nerve exposure operation as the SNI group except for nerve ligation.

Protein-tyrosine kinase 2-beta (PYK2)

Target Gene

Inflammatory response [ICD-11: MG46]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[168]
Responsed Disease	Inflammatory response [ICD-11: MG46]
In-vitro Model	RAW 264.7	Mouse leukemia	Mus musculus	CVCL_0493

Pseudorabies Virus (PRV)

Target Gene

Rabies [ICD-11: 1C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[169]
Responsed Disease	Rabies [ICD-11: 1C82]
Responsed Drug	3-deazidenosine		Investigative	Drug Info
Target Regulation	Up regulation
In-vitro Model	PK-15	N.A.	Sus scrofa	CVCL_2160

Ras-related protein R-Ras (RRAS)

Target Gene

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[170]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Down regulation
In-vitro Model	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	J82	Bladder carcinoma	Homo sapiens	CVCL_0359
	TCCSUP	Bladder carcinoma	Homo sapiens	CVCL_1738
	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
In-vivo Model	A total of 16 male, 4- to 6-week-old BALB/c nude mice weighing 18-26 g, were purchased from the Institute of Model Animals, Nanjing University and raised in a specific pathogen-free (SPF) environment for the xenograft model. The mice were raised in animal individually ventilated cage (IVC cages) with a room temperature of 24°C and relative humidity of 70% and the air exchange rate was 15 times/h. The mice could drink filtered tap water and commercial feed ad libitum under a strict 12-h light/dark cycle. The animal laboratory was cleaned twice one day and sterilized with ultraviolet light for 1 h each week. Each mouse was injected with 100 μl PBS containing 1×10⁶ T24 cell lines expressing either LV-NC or LV-shMETTL3 subcutaneously under the right armpit. Tumor volumes were recorded on day 7 after the injection and then measured each week. At day 28, the mice were sacrificed by cervical dislocation following the inhalation of 3% isoflurane anesthesia and the death of the mice was confirmed by respiratory arrest. Tumor weights were also compared. The data from each group of mice are expressed as the mean ± standard deviation (SD).

Ras-related protein Rab-5A (RAB5A)

Target Gene

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[171]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]
Target Regulation	Down regulation
In-vivo Model	Briefly, 4 × 10⁶ transfected HCT116 cells or 8 × 10⁶ transfected SW480 cells in 0.1 mL PBS were injected into mice subcutaneously, and these mice were randomly divided into the experimental and control group.

Retinoic acid receptor RXR-alpha (RXRA)

Target Gene

Autoimmune liver disease [ICD-11: DB96]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[172]
Responsed Disease	Autoimmune liver disease [ICD-11: DB96.0]
Target Regulation	Down regulation

RNA demethylase ALKBH5 (ALKBH5)

Target Gene

Diabetic encephalopathy [ICD-11: 8E47]

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	Diabetic encephalopathy [ICD-11: 8E47]

RNA-binding protein Nova-2 (NOVA2)

Target Gene

Hepatic fibrosis/cirrhosis [ICD-11: DB93]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[173]
Responsed Disease	Hepatic fibrosis/cirrhosis [ICD-11: DB93]
Target Regulation	Down regulation

Runt-related transcription factor 1 (RUNX1)

Target Gene

Hematological disorders [ICD-11: 3C0Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[43]
Responsed Disease	Hematological disorders [ICD-11: 3C0Z]
Target Regulation	Down regulation

Semaphorin-3F (SEMA3F)

Target Gene

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[174]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
In-vitro Model	RWPE-1	Normal	Homo sapiens	CVCL_3791
	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
	22Rv1	Prostate carcinoma	Homo sapiens	CVCL_1045
	LNCaP	Prostate carcinoma	Homo sapiens	CVCL_0395
	LNCaP C4-2B	Prostate carcinoma	Homo sapiens	CVCL_4784
	VCaP	Prostate carcinoma	Homo sapiens	CVCL_2235
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	All the animal studies and protocols followed the institutional guidelines of the First Affiliated Hospital, School of Medicine, Zhejiang University.

Serine/threonine-protein kinase LATS1 (LATS1)

Target Gene

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[175]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Down regulation
In-vitro Model	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	T-47D	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	BT-474	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	MDA-MB-468	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
In-vivo Model	All animal experiments were approved by the Institutional Animal Care and Use Committee of Southern Medical University. Breast cancer cells (5 × 10⁶) were implanted into the subcutaneous axilla of the forelimb of 3-4-week-old BALB/c nude mice. Seven days after transplantation, the diameter of the tumors was measured, and the tumors were removed after three weeks.

Serine/threonine-protein kinase PAK 6 (PAK5)

Target Gene

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[176]
Responsed Disease	Cervical cancer [ICD-11: 2C77]
Target Regulation	Down regulation
In-vitro Model	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
In-vivo Model	Tumor xenograft models were established, with each group consisting of 5 mice (n = 5 per group), including ALKBH5, ALKBH5/shPAK5, NC, shCon, shPAK5, shALKBH5, and shALKBH5. Subcutaneous injections of stably transfected HeLa cells (2.0 × 10⁶ cells) were administered into the armpit region of the nude mice. The tumor volume was regularly monitored using the formula: volume = 0.5 × length × width2. After 5 weeks, the mice were euthanized and the weight of tumor was measured. In the lung metastasis models, which were conducted in nude mice, the groups consisted of 5 mice per group, similar to the tumor xenograft models. In these models, HeLa cells (2.0 × 10⁶) that had been stably transfected were injected into the mice through the tail vein. After 5 weeks, the mice were euthanized. The lung tissues were excised, photographed, and fixed in 4% paraformaldehyde for H&E staining.

Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform (PPP2CA)

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				[177]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
In-vitro Model	HGC-27	Gastric carcinoma	Homo sapiens	CVCL_1279
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
In-vivo Model	We injected 2 × 10⁶ stably infected GC cells subcutaneously into each dorsal flank of mice (n = 6). After 4 weeks, each histologically intact tumor was removed, weighed and photographed. To construct the model of mice pulmonary metastasis, we injected 2 × 10⁶ stably infected GC cells into the tail vein of the mice (n = 5).

Taurine up-regulated 1 protein (TUG1)

Target Gene

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[178]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Down regulation

testis expressed 41 (TEX41)

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		[179]
Responsed Disease	Renal cell carcinoma [ICD-11: 2C90]
Target Regulation	Up regulation

Tnfrsf2

Target Gene

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[180]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Target Regulation	Down regulation
Pathway Response	Signaling pathways regulating pluripotency of stem cells			hsa04550
Cell Process	mRNA decay
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
In-vivo Model	THP-1 cells transduced with CTL or KD lentiviruses were tail vein injected into non-irradiated 12 week-old female non-obese diabetic (NOD)/LtSz-severe combined immune-deficiency (SCID) IL-2Rγcnull (NSG) mice (1x10⁶ cells per 200 uL per mouse).
Response Summary	Acute myeloid leukemia (AML) is an aggressive clonal disorder of hematopoietic stem cells (HSCs) and primitive progenitors that blocks their myeloid differentiation, generating self-renewing leukemic stem cells (LSCs). YTHDF2 decreases the half-life of diverse m6A transcripts that contribute to the overall integrity of LSC function, including the tumor necrosis factor receptor Tnfrsf2, whose upregulation in Ythdf2-deficient LSCs primes cells for apoptosis.

Transcription factor E2F6 (E2F6)

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		[112]
Responsed Disease	Liver cancer [ICD-11: 2C12]
Target Regulation	Down regulation

Transcription factor GATA-6 (GATA6)

Target Gene

Injury of other or unspecified intrathoracic organs [ICD-11: NB32]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[181]
Responsed Disease	Injury of other or unspecified intrathoracic organs [ICD-11: NB32.3]
Target Regulation	Down regulation
In-vitro Model	BEAS-2B	Normal	Homo sapiens	CVCL_0168
In-vivo Model	To perform in vivo plasmid transfection, the researchers mixed the pcDNA3.1-EGFP-METTL3 plasmid with in vivo jetPEI (Polyplus-transfection; Illkirch) per the manufacturer's guidelines. They mixed 40 μg of plasmid nucleic acid in 5% glucose (25 μl) with 6.4 μl of jetPEI solution in 5% glucose (25 μl) to obtain a final nitrogen and phosphorus ratio of 8. The mixture was incubated at room temperature for 30 minutes to form stable complexes before tracheal intubation of mice.

Transcription factor SOX-9 (SOX9)

Target Gene

Rheumatoid arthritis [ICD-11: FA20]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[182]
Responsed Disease	Rheumatoid arthritis [ICD-11: FA20]

Tripartite motif-containing protein 72 (TRIM72)

Target Gene

Preeclampsia [ICD-11: JA23]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[183]
Responsed Disease	Preeclampsia [ICD-11: JA23]
Target Regulation	Down regulation

Tyrosine-protein kinase JAK1 (JAK1)

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				[184]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation
In-vitro Model	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
In-vivo Model	BGC-823 (3 × 10⁶) cells that stably expressed or silenced ALKBH5 and LINC00659 and their paired control cells were injected into the left side of each mouse. For cell metastasis experiments in vivo, BGC-823 (3 × 10⁶) cells that stably overexpressed or silenced ALKBH5 and LINC00659 and their paired control cells were injected through tail vein.

Ubiquitin carboxyl-terminal hydrolase 38 (USP38)

Target Gene

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[185]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Target Regulation	Up regulation
In-vitro Model	SV-HUC-1	Normal	Homo sapiens	CVCL_3798
In-vivo Model	BALB/c nude mice were purchased from the Slac Laboratories (Shanghai, China) and randomly divided into two groups. The xenograft mouse model was generated via tail-vein injection of METTL14-expressing T24 cells (5 × 10⁵ cells per mouse) into experimental mice while those injected with pcDNA3.1 empty vector transfected cells as control.

Voltage-dependent L-type calcium channel subunit alpha-1C (CACNA1C)

Target Gene

Supraventricular tachyarrhythmia [ICD-11: BC81]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[186]
Responsed Disease	Supraventricular tachyarrhythmia [ICD-11: BC81.3]
In-vivo Model	Under isoflurane anesthesia, bipolar leads were inserted into the right atrial (RA) appendage and connected to pacemakers. Following a 24-h recovery, the atrial pacemaker was programmed to pace the RA appendage at atrial tachycardia pacing for 2 weeks.

Unspecific 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				[187]
Responsed Disease	Solid tumour/cancer [ICD-11: 2A00-2F9Z]
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	HEK293T	Normal	Homo sapiens	CVCL_0063
	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	HEK293-FT	Normal	Homo sapiens	CVCL_6911
In-vivo Model	Stable H1299 cell lines diluted into 100uL were injected subcutaneously into 5-week-old nude mice (n = 5) at the final concentration of 3 × 10⁶ cells. Mice were sacrificed 4 weeks later, and tumors were weighed and photographed.
Response Summary	SUMOylation of YTHDF2 has little impact on its ubiquitination and localization, but significantly increases its binding affinity of m6A-modified mRNAs and subsequently results in deregulated gene expressions which accounts for cancer progression.

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				[188]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Down regulation
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
Response Summary	YTHDF2 mRNA in gastric cancer was significantly higher than that in the normal tissues.Knockdown of YTHDF2 in MGC-803 cells inhibits cell proliferation and promotes apoptosis.

Liver cancer [ICD-11: 2C12]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[189]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Responsed Drug	Teniposide		Approved	Drug Info
Pathway Response	Nucleotide excision repair			hsa03420
	mTOR signaling pathway			hsa04150
Cell Process	DNA repair
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
In-vivo Model	To establish a tumour model, C57BL/6 mice were intraperitoneal injected with 25 mg/kg diethylnitrosamine at 2 weeks of age.
Response Summary	The m6A model includes LRPPRC, YTHDF2, KIAA14219, and RBM15B, classified A-hepatocellular carcinoma patients into high/low-risk subtypes. The expression of Immunosuppressive cytokines DNMT1/EZH2 was up-regulated in A-hepatocellular carcinoma patients, and teniposide can be a potential therapeutic drug for A-hepatocellular carcinoma.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene				[190]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
Response Summary	MIR145 modulates m6A levels by targeting the 3'-UTR of YTHDF2 mRNA in hepatocellular carcinoma 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				[192]
Responsed Disease	Lung squamous cell carcinoma [ICD-11: 2C25.2]
Pathway Response	mTOR signaling pathway			hsa04150
	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation
	Cell invasion
In-vitro Model	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630
	NCI-H226	Pleural epithelioid mesothelioma	Homo sapiens	CVCL_1544
In-vivo Model	The mice were randomly divided into two groups which were inoculated with stable YTHDF2-expressing LUSC cells and the vector LUSC cells. A total of 5 × 10⁶ of the cells were suspended in 0.1 ml of PBS and then injected subcutaneously into the flanks of mice.
Response Summary	High-YTHDF2 expression predicted a worse prognosis of LUSC, while hypoxia-mediated YTHDF2 overexpression promotes lung squamous cell carcinoma progression by activation of the mTOR/AKT signaling pathway.

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				[193]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Cell Process	Cell proliferation and migration
	Cell apoptosis
In-vitro Model	SK-OV-3	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
Response Summary	YTHDF2 and microRNA 145, as two crucial m6A regulators, were involved in the progression of epithelial ovarian cancer by indirectly modulating m6A levels.

Endometrial cancer [ICD-11: 2C76]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[194]
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
In-vitro Model	RL95-2	Endometrial adenosquamous carcinoma	Homo sapiens	CVCL_0505
	Ishikawa	Endometrial adenocarcinoma	Homo sapiens	CVCL_2529
	HHUA	Endometrial adenocarcinoma	Homo sapiens	CVCL_3866
	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293
Response Summary	YTHDF2 expression can accurately assess the depth of myometrial invasion (DMI) in EMAC when EMAC coexists with adenomyosis.

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[195]
Responsed Disease	Prostate cancer [ICD-11: 2C82]
Cell Process	Cell proliferation
	Cell migration
In-vitro Model	DU145	Prostate carcinoma	Homo sapiens	CVCL_0105
	PC-3	Prostate carcinoma	Homo sapiens	CVCL_0035
Response Summary	YTHDF2 and miR-493-3p provide new insights into the carcinogenesis and new potential therapeutic targets for PCa.

Hematological disorders [ICD-11: 3C0Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[196]
Responsed Disease	Hematological disorders [ICD-11: 3C0Z]
Cell Process	RNA stability
In-vitro Model	Hematopoietic stem cells (Hematopoietic stem cells)
In-vivo Model	Utilized three Cre transgenic mouse lines (Mx1-Cre, Ert-Cre and Vav-Cre) to cross with Ythdf2^fl/fl mice to deplete the expression of YTHDF2 specifically in adult HSCs of mouse bone marrow (BM), respectively.
Response Summary	YTHDF2 deletion uniquely affects the homeostasis of HSPCs.

Lupus erythematosus [ICD-11: 4A40]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[197]
Responsed Disease	Lupus erythematosus [ICD-11: 4A40]
Response Summary	These findings suggested decreased YTHDF2 that was associated with disease activity play an important role in the pathogenesis of SLE, METTL14 and ALKBH5 were concomitantly decreased.

Liver disease [ICD-11: DB9Z]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[198]
Responsed Disease	Liver disease [ICD-11: DB9Z]
Pathway Response	PPAR signaling pathway	hsa03320
Cell Process	Fatty degeneration
In-vivo Model	A total of 24 male mice were randomly allocated to LFD (low-fat diet), LFDR (low-fat diet + resveratrol), HFD (high-fat diet), and HFDR (high-fat diet + resveratrol) groups for 12 weeks (n = 6/group).
Response Summary	The beneficial effect of resveratrol on lipid metabolism disorder under HFD is due to a decrease of m6A RNA methylation and an increase of PPARalpha mRNA, providing mechanistic insights into the function of resveratrol in alleviating the disturbance of lipid metabolism in mice. The resveratrol in HFD increased the transcript levels of methyltransferase like 3 (METTL3), alkB homolog 5 (ALKBH5), fat mass and obesity associated protein (FTO), and YTH domain family 2 (YTHDF2), whereas it decreased the level of YTH domain family 3 (YTHDF3) and m6A abundance in mice liver.

Chondropathies [ICD-11: FB82]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[199]
Responsed Disease	Steroid-induced necrosis of the femoral head [ICD-11: FB82.1]

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		[200]
Responsed Disease	Male infertility [ICD-11: GB04]
Cell Process	Apoptosis in germ cells
In-vitro Model	Spermatogenic cells (Prepared from undifferentiated mouse spermatogonial cells)
In-vivo Model	The knockout first allele was converted into a conditional allele by crossing Ythdf2 knockout first mice with Flp deleter mice. The resulting floxed Ythdf2 mice were crossed with Vasa-GFPCre knock-in mice to allow specific knockout of Ythdf2 in germ cells.
Response Summary	Germ cell-specific Ythdf2 mutants (Ythdf2-vKO) at a C57BL/6J background and demonstrated that YTHDF2 is essential for mouse spermatogenesis and fertility. Demonstrates the fundamental role of YTHDF2 during mouse spermatogenesis and provides a potential candidate for the diagnosis of male infertility with the oligoasthenoteratozoospermia syndrome.

C-X-C chemokine receptor type 4 (CXCR4)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Testis	Mus musculus
Treatment: YTHDF2 knockout mice testis Control: Mice testis		GSE147574
Regulation		logFC: 7.39E-01 p-value: 4.60E-02
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 2.20E+00	GSE49339

PMID31239444-anti-PD1 antibody [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[3]
Responsed Disease	Melanoma		ICD-11: 2C30	Disease Info
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	mRNA decay
In-vitro Model	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
	CHL-1	Melanoma	Homo sapiens	CVCL_1122
	624-mel	Melanoma	Homo sapiens	CVCL_8054
	NHEM (Normal Human Epidermal Melanocytes)
	SK-MEL-30	Cutaneous melanoma	Homo sapiens	CVCL_0039
	WM115	Melanoma	Homo sapiens	CVCL_0040
	WM35	Melanoma	Homo sapiens	CVCL_0580
	WM3670	Melanoma	Homo sapiens	CVCL_6799
	WM793	Melanoma	Homo sapiens	CVCL_8787
In-vivo Model	When the tumors reached a volume of 80-100 mm³, mice were treated with anti-PD-1 or isotype control antibody (200 ug/mouse) by i.p. injection, every other day for three times. For IFNγ blockade treatment, C57BL/6 mice were treated with anti-IFNγ antibody or isotype control IgG (250 ug/mouse) every other day after tumor cell inoculation.
Response Summary	These findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade reduces the resistance to immunotherapy in melanoma. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), C-X-C chemokine receptor type 4 (CXCR4), and SOX10, leading to increased RNA decay through the m6A reader YTHDF2.

Ephrin type-B receptor 3 (EPHB3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	Mouse-cerebellum granule cell	Mus musculus
Treatment: YTHDF2 knockdown mouse-cerebellum granule cell Control: Wild type mouse-cerebellum granule cell		GSE153688
Regulation		logFC: -6.25E-01 p-value: 1.90E-03
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.21E+00	GSE49339

Temozolomide [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	Glioblastoma		ICD-11: 2A00.00	Disease Info
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	RNA stability
In-vitro Model	T98G	Glioblastoma	Homo sapiens	CVCL_0556
In-vitro Model	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
In-vivo Model	5 × 10⁶ infected T98G cells (LV-NC or LV-YTHDF2) were injected into the flanks of mice through subcutaneous.
Response Summary	YTHDF2 enhanced TMZ resistance in GBM by activation of the PI3K/Akt and NF-Kappa-B signalling pathways via inhibition of Ephrin type-B receptor 3 (EPHB3) and TNFAIP3.

Myc proto-oncogene protein (MYC)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	GSC11 cell line	Homo sapiens
Treatment: siYTHDF2 GSC11 cells Control: siControl GSC11 cells		GSE142825
Regulation		logFC: 8.94E-01 p-value: 8.57E-07
More Results	Click to View More RNA-seq Results
*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.40E+00	GSE49339

Linsitinib [Phase 3]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[11]
Responsed Disease	Glioma	ICD-11: 2A00.0	Disease Info
Target Regulation	Up regulation
Pathway Response	RNA degradation		hsa03018
Cell Process	RNA stability
In-vitro Model	()
	HNP1 (A human neural progenitor cell)
	NHA (Normal human astrocytes)
	NSC11 (Pluripotent derived neural progenitor cell)
In-vivo Model	For in vivo drug treatment studies, intracranial xenografts were generated by implanting 5000 patient-derived GSCs (387 and 4121) into the right cerebral cortex of NSG mice as described above.
Response Summary	The m6A reader YTHDF2 stabilized Myc proto-oncogene protein (MYC) mRNA specifically in cancer stem cells. Given the challenge of targeting MYC, YTHDF2 presents a therapeutic target to perturb MYC signaling in glioblastoma. The IGF1/IGF1R inhibitor linsitinib preferentially targeted YTHDF2-expressing cells, inhibiting GSC viability without affecting NSCs and impairing in vivo glioblastoma growth. YTHDF2 links RNA epitranscriptomic modifications and GSC growth, laying the foundation for the YTHDF2-MYC-IGFBP3 axis as a specific and novel therapeutic target in glioblastoma.

Tamoxifen [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
Pathway Response	MAPK signaling pathway			hsa04010
Cell Process	Epithelial-to-mesenchymal transition
Cell Process	Cell apoptosis
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MBA-MD-231 (Human breast cancer cell)
	MYC-ER HMEC (Human mammary epithelial cells expressing a MYC estrogen receptor fusion)
	SK-BR-3	Breast adenocarcinoma	Homo sapiens	CVCL_0033
In-vivo Model	To induce recombination at 8 weeks of age both CAG-CreERT;Ythdf2^fl/fl and Ythdf2^fl/fl littermates were injected with 75mg/kg body weight tamoxifen dissolved in corn oil daily for 5 days.
Response Summary	LCAT3 upregulation is attributable to m6A modification mediated by METTL3, leading to LCAT3 stabilization. Treated cells with tamoxifen to induce MYC activity. Highlights the therapeutic potential of RBPs by uncovering a critical role for YTHDF2 in counteracting the global increase of mRNA synthesis in Myc proto-oncogene protein (MYC)-driven breast cancers.

Nucleobindin-1 (NUCB1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2*
Cell Line	B18-hi B cell line	Mus musculus
Treatment: YTHDF2 knockout B18-hi B cells Control: Wild type B18-hi B cells		GSE189819
Regulation		logFC: 6.95E-01 p-value: 1.62E-02
More Results	Click to View More RNA-seq Results

Gemcitabine [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[30]
Responsed Disease	Pancreatic ductal adenocarcinoma		ICD-11: 2C10.0	Disease Info
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Cell proliferation
Cell Process	Cell autophagy
In-vitro Model	SW1990	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1723
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	HEK293T	Normal	Homo sapiens	CVCL_0063
	CFPAC-1	Cystic fibrosis	Homo sapiens	CVCL_1119
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
In-vivo Model	5 × 10⁶ SW1990 cells expressing NUCB1 (oeNUCB1) or control vector (oeNC) were injected subcutaneously.
Response Summary	METTL3-mediated m6A modification on Nucleobindin-1 (NUCB1) 5'UTR via the reader YTHDF2 as a mechanism for NUCB1 downregulation in PDAC. This study revealed crucial functions of NUCB1 in suppressing proliferation and enhancing the effects of gemcitabine in pancreatic cancer cells.

PI3-kinase subunit beta (PIK3CB)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.28E+00	GSE49339

AZD6482 [Terminated]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[42]
Responsed Disease	Pancreatic cancer		ICD-11: 2C10	Disease Info
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glucose metabolism
In-vitro Model	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
In-vivo Model	Established cohorts of mice bearing tumour xenografts driven by PTEN-deficient BxPC-3 and PANC-1 cells with PIK3CB overexpression. When tumours grew to ~300 mm³, mice were grouped and administered with vehicle (DMSO) or KIN-193 via intraperitoneal injection (20 mg/kg) once daily.
Response Summary	N6-methyladenosine mRNA methylation of PIK3CB regulates AKT signalling to promote PTEN-deficient pancreatic cancer progression. Rs142933486 is significantly associated with the overall survival of PDAC by reducing the PIK3CB m6A level, which facilitated its mRNA and protein expression levels mediated by the m6A 'writer' complex (METTL13/METTL14/WTAP) and the m6A 'reader' YTHDF2. KIN-193, a PI3-kinase subunit beta (PIK3CB)-selective inhibitor, is shown to serve as an effective anticancer agent for blocking PTEN-deficient PDAC.

TNF alpha-induced protein 3 (TNFAIP3)

Target Gene

*Representative RIP-seq result supporting the interaction between the target gene and YTHDF2*
Cell Line	Hela	Homo sapiens
Regulation	logFC: 1.94E+00	GSE49339

Temozolomide [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	Glioblastoma		ICD-11: 2A00.00	Disease Info
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	RNA stability
In-vitro Model	T98G	Glioblastoma	Homo sapiens	CVCL_0556
In-vitro Model	LN-229	Glioblastoma	Homo sapiens	CVCL_0393
In-vivo Model	5 × 10⁶ infected T98G cells (LV-NC or LV-YTHDF2) were injected into the flanks of mice through subcutaneous.
Response Summary	YTHDF2 enhanced TMZ resistance in GBM by activation of the PI3K/Akt and NF-Kappa-B signalling pathways via inhibition of EPHB3 and TNF alpha-induced protein 3 (TNFAIP3).

ATP-binding cassette sub-family C member 10 (ABCC10)

Target Gene

Gefitinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[46]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Down regulation
Pathway Response	ABC transporters			hsa02010
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In-vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
In-vivo Model	Mice were randomized into three groups (n = 7/group), 1 × 10⁷ PC9 cells absorbed exosomes were subcutaneously injected into the Bilateral groin of mice. Treatment began 1 week following injection, the mice were intraperitoneally injected with gefitinib (30 mg/kg/day).
Response Summary	Not only FTO knockdown enhanced the gefitinib sensitivity of GR cells but also FTO reduction in donor exosomes alleviated the acquired resistance of recipient non-small cell lung cancer PC9 cells. FTO/YTHDF2/ATP-binding cassette sub-family C member 10 (ABCC10) axis played a role in intercellular transmission of GR cell-derived exosome-mediated gefitinib resistance.

Axin-1 (AXIN1)

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				[48]
Responsed Disease	Cervical cancer		ICD-11: 2C77	Disease Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
Cell Process	Epithelial-mesenchymal transition
In-vitro Model	SiHa	Cervical squamous cell carcinoma	Homo sapiens	CVCL_0032
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Ect1/E6E7	Normal	Homo sapiens	CVCL_3679
	Ca Ski	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	C-33 A	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1094
Response Summary	YTHDF2 interference could suppress the EMT of cervical cancer cells and enhance cisplatin chemosensitivity by regulating Axin-1 (AXIN1).

BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)

Target Gene

Chromium [Approved]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene		[51]
Target Regulation	Down regulation

Cyclic AMP-dependent transcription factor ATF-4 (ATF4)

Target Gene

Asparagine inhibitor [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition.

Chloroquine [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.

Meclofenamate sodium [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.

Rapamycin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.

CB-839 [Phase 2]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition.

GLS-IN-968 [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition.

Cyclin-A2 (CCNA2)

Target Gene

Epigallocatechin gallate [Phase 3]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[58]
Responsed Disease	Obesity		ICD-11: 5B81	Disease Info
Target Regulation	Down regulation
Cell Process	Adipogenesis
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Response Summary	m6A-dependent Cyclin-A2 (CCNA2) and CDK2 expressions mediated by FTO and YTHDF2 contributed to EGCG-induced adipogenesis inhibition.

Cyclin-dependent kinase 2 (CDK2)

Target Gene

Epigallocatechin gallate [Phase 3]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[58]
Responsed Disease	Obesity		ICD-11: 5B81	Disease Info
Target Regulation	Down regulation
Cell Process	Adipogenesis
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Response Summary	m6A-dependent CCNA2 and Cyclin-dependent kinase 2 (CDK2) expressions mediated by FTO and YTHDF2 contributed to EGCG-induced adipogenesis inhibition.

FB23-2 [Investigative]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[61]
Responsed Disease	Diabetic retinopathy	ICD-11: 9B71.0	Disease Info
Target Regulation	Down regulation

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				[62]
Responsed Disease	Intrahepatic cholangiocarcinoma		ICD-11: 2C12.10	Disease Info
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell proliferation
	Arrest cell cycle at G0/G1 phase
In-vitro Model	HuCC-T1	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_0324
	RBE	Intrahepatic cholangiocarcinoma	Homo sapiens	CVCL_4896
	HCCC-9810 (The intrahepatic cholangiocarcinoma cell lines (HCCC-9810) were purchased from Cellcook Co., Ltd. (Guangzhou, China).)
	HIBEC (The normal intrahepatic bile duct cell line (HIBEC) were purchased from Cellcook Co., Ltd. (Guangzhou, China).)
In-vivo Model	For tumour xenograft models, 1 × 10⁷ HuCC-T1 cells in knockdown group or control group were implanted into the right flank of 5-week-old female nude mice. The volumes of tumour were recorded every 4 days by calliper. The volumes were calculated as length × width2/2. For patient-derived xenograft (PDX) model (PDX0075), ICC tissues from a patient, who relapsed in 6 months after R0 resection and subsequent chemotherapy with cisplatin and gemcitabine, were diced into 3 mm³ pieces and transplanted subcutaneously into the right flank of 5-week-old female B-NDG mice.
Response Summary	The role of YTHDF2 in tumourigenesis and cisplatin-desensitising function by promoting the degradation of Cyclin-dependent kinase inhibitor 1B (CDKN1B/p27) mRNA in an m6 A-dependent manner. YTHDF2 exhibits tumour oncogenic and cisplatin-desensitising properties, which offer insight into the development of novel combination therapeutic strategies for intrahepatic cholangiocarcinoma.

Death-associated protein kinase 3 (DAPK3)

Target Gene

Gemcitabine [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[67]
Responsed Disease	Gallbladder cancer	ICD-11: 2C13	Disease Info
Target Regulation	Down regulation
In-vivo Model	Male BALB/c nude mice (6 weeks old) were used for xenograft experiments. A 150 μL-cell suspension containing 5 × 10⁶ cells was injected s.c. into each nude mouse. Tumor volumes were measured every 4 days for 1 month. To evaluate chemosensitivity to gemcitabine, mice were i.p. injected with gemcitabine (50 mg/kg) every 4 days when the tumor volume reached 100 mm3.Male NOD/SCID mice (6 weeks old) were used for lung metastasis experiments. A 150 μL-cell suspension containing 5 × 10⁵ cells was injected i.v. into the tail vein of each mouse. After 1 month, the lungs were harvested and photographed, and the number of metastatic lesions was calculated.

DNA replication licensing factor MCM5 (MCM5)

Target Gene

OSMI-1 [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[69]
Responsed Disease	Liver hepatocellular carcinoma		ICD-11: 2C12.02	Disease Info
Target Regulation	Up regulation
In-vitro Model	HepAD38	Hepatoblastoma	Homo sapiens	CVCL_M177
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	HEK293	Normal	Homo sapiens	CVCL_0045
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	For the xenograft implantation model, 2 × 10⁶ MHCC-97H cells were subcutaneously injected into the flank of nude mice.

Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1)

Target Gene

Rapamycin [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[72]
Responsed Disease	Oral squamous cell carcinoma	ICD-11: 2B6E.0	Disease Info
Target Regulation	Down regulation
Pathway Response	Autophagy		hsa04140
Cell Process	Cell autophagy
Response Summary	Rapamycin inhibited FTO activity, and directly targeted Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) transcripts and mediated their expression in an m6A-dependent manner in oral squamous cell carcinoma. After FTO silencing, YTHDF2 captured eIF4G1 transcripts containing m6A, resulting in mRNA degradation and decreased expression of eIF4G1 protein, thereby promoting autophagy and reducing tumor occurrence.

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

Target Gene

Chromium [Approved]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene		[51]
Target Regulation	Down regulation

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

Target Gene

Gefitinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[89]
Responsed Disease	Lung cancer		ICD-11: 2C25	Disease Info
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
	PC-9/GR2	Lung adenocarcinoma	Homo sapiens	CVCL_DI29
	HCC827/GR	N.A.	Homo sapiens	CVCL_E7R9
In-vivo Model	To establish xenograft models, five-week-old male mice were orthotopically injected with the same number of the PC9/GR cells. Tumours had developed after 4 days, at which time the xenografted mice were randomly divided into the following two experimental groups (each group with 6 mice): (1) the control group and (2) the gefitinib group.

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

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				[99]
Responsed Disease	Insulin resistance		ICD-11: 5A44	Disease Info
In-vitro Model	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926

Programmed cell death 1 (PD-1)

Target Gene

PMID31239444-anti-PD1 antibody [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[3]
Responsed Disease	Melanoma		ICD-11: 2C30	Disease Info
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	mRNA decay
In-vitro Model	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
	CHL-1	Melanoma	Homo sapiens	CVCL_1122
	624-mel	Melanoma	Homo sapiens	CVCL_8054
	NHEM (Normal Human Epidermal Melanocytes)
	SK-MEL-30	Cutaneous melanoma	Homo sapiens	CVCL_0039
	WM115	Melanoma	Homo sapiens	CVCL_0040
	WM35	Melanoma	Homo sapiens	CVCL_0580
	WM3670	Melanoma	Homo sapiens	CVCL_6799
	WM793	Melanoma	Homo sapiens	CVCL_8787
In-vivo Model	When the tumors reached a volume of 80-100 mm³, mice were treated with anti-PD-1 or isotype control antibody (200 ug/mouse) by i.p. injection, every other day for three times. For IFNγ blockade treatment, C57BL/6 mice were treated with anti-IFNγ antibody or isotype control IgG (250 ug/mouse) every other day after tumor cell inoculation.
Response Summary	These findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade reduces the resistance to immunotherapy in melanoma. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including Programmed cell death 1 (PD-1) (PDCD1), CXCR4, and SOX10, leading to increased RNA decay through the m6A reader YTHDF2.

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

Target Gene

Bacillus Calmette [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[101]
Responsed Disease	Bladder cancer		ICD-11: 2C94	Disease Info
Target Regulation	Down regulation
In-vitro Model	MGH-U3	Bladder carcinoma	Homo sapiens	CVCL_9827
	SW780	Bladder carcinoma	Homo sapiens	CVCL_1728
	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
	T24	Bladder carcinoma	Homo sapiens	CVCL_0554
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
In-vivo Model	For xenograft studies, female mice between 4 and 6 weeks of age were used. Monoclonal cell lines showing a nearly complete absence of Ythdf2 and Ddx58 were used for in vivo experimentation. Mice were implanted with 2 × 10⁶ MGHU3 cells resuspended in 100 μL of Matrigel Matrix High Concentration (354248) and PBS mixture subcutaneously into the right flanks. Subcutaneous tumor growth was measured weekly by calipers, and the volume was calculated using the formula: volume = (length × width2)/2.

Serine/threonine-protein kinase mTOR (MTOR)

Target Gene

Asparagine inhibitor [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition.

Chloroquine [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.

Meclofenamate sodium [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.

Rapamycin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.

CB-839 [Phase 2]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition.

GLS-IN-968 [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[56]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	Autophagy			hsa04140
Cell Process	RNA decay
	Cell growth and death
	Cell autophagy
In-vitro Model	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
Response Summary	In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition.

Serine/threonine-protein kinase ULK1 (ULK1/ATG1)

Target Gene

Rapamycin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[103]
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	RNA stability
	Cell autophagy
In-vitro Model	HEK293T	Normal	Homo sapiens	CVCL_0063
	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
Response Summary	The m6A changes caused by FTO influence the stability of ULK1 transcripts, likely through a YTHDF2-dependent manner.Under both basal and rapamycin-induced autophagy conditions, depletion of FTO significantly reduced the formation of GFP-LC3B puncta. The level of p62/SQSTM1 (an autophagy substrate) was higher in FTO-knockdown cells than that in control cells. FTO specifically upregulates the Serine/threonine-protein kinase ULK1 (ULK1) protein abundance. ULK1 mRNA undergoes m6A modification in the 3'-UTR and the m6A-marked ULK1 transcripts can further be targeted for degradation by YTHDF2.

Serum response factor (SRF)

Target Gene

Tislelizumab [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[104]
Responsed Disease	Glioblastoma		ICD-11: 2A00.00	Disease Info
In-vitro Model	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022

Stimulator of interferon genes protein (STING1)

Target Gene

Fluorene-9-bisphenol [Investigative]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene		[108]
Target Regulation	Up regulation

Suppressor of cytokine signaling 3 (SOCS3)

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				[110]
Responsed Disease	Human skin lesions		ICD-11: ME60	Disease Info
Target Regulation	Down regulation
Pathway Response	JAK-STAT signaling pathway			hsa04630
In-vitro Model	HaCaT	Normal	Homo sapiens	CVCL_0038

Transcription factor SOX-10 (SOX10)

Target Gene

PMID31239444-anti-PD1 antibody [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[3]
Responsed Disease	Melanoma		ICD-11: 2C30	Disease Info
Target Regulation	Down regulation
Pathway Response	PD-L1 expression and PD-1 checkpoint pathway in cancer			hsa05235
Cell Process	mRNA decay
In-vitro Model	B16-F10	Mouse melanoma	Mus musculus	CVCL_0159
	CHL-1	Melanoma	Homo sapiens	CVCL_1122
	624-mel	Melanoma	Homo sapiens	CVCL_8054
	NHEM (Normal Human Epidermal Melanocytes)
	SK-MEL-30	Cutaneous melanoma	Homo sapiens	CVCL_0039
	WM115	Melanoma	Homo sapiens	CVCL_0040
	WM35	Melanoma	Homo sapiens	CVCL_0580
	WM3670	Melanoma	Homo sapiens	CVCL_6799
	WM793	Melanoma	Homo sapiens	CVCL_8787
In-vivo Model	When the tumors reached a volume of 80-100 mm³, mice were treated with anti-PD-1 or isotype control antibody (200 ug/mouse) by i.p. injection, every other day for three times. For IFNγ blockade treatment, C57BL/6 mice were treated with anti-IFNγ antibody or isotype control IgG (250 ug/mouse) every other day after tumor cell inoculation.
Response Summary	These findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade reduces the resistance to immunotherapy in melanoma. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and Transcription factor SOX-10 (SOX10), leading to increased RNA decay through the m6A reader YTHDF2.

LINC00902 (TUSC7)

Target Gene

Erlotinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[117]
Responsed Disease	Lung adenocarcinoma		ICD-11: 2C25.0	Disease Info
Target Regulation	Down regulation
Pathway Response	Notch signaling pathway			hsa04330), EGFR tyrosine kinase inhibitor resistance
In-vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
In-vivo Model	Control vector, TUSC7 knockout, FLI-06 treated H1975 cells (1*10⁷) cells were suspended in 100 uL of serum-free DMEM medium (Hyclone, USA), mixed with matrix gel (Corning, USA), and then were injected subcutaneously. The changes in the tumor size were recorded every 3 or 5 days.
Response Summary	In lung adenocarcinoma, The miR-146a/Notch signaling was sustained highly activated in a m6A dependent manner, and the m6A regulator of YTHDF2 suppressed LINC00902 (TUSC7), both of which contributed to the resistant features. Functionally, the sponge type of TUSC7 regulation of miR-146a inhibited Notch signaling functions, and affected the cancer progression and stem cells' renewal in Erlotinib resistant PC9 cells (PC9ER) and Erlotinib resistant HCC827 cells (HCC827ER) cells.

Long intergenic non-protein coding RNA 1273 (LINC01273)

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				[118]
Responsed Disease	Hepatocellular carcinoma		ICD-11: 2C12.02	Disease Info
Target Regulation	Down regulation
In-vitro Model	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vitro Model	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
Response Summary	Long intergenic non-protein coding RNA 1273 (LINC01273) was modified with m6A, METTL3 increased LINC01273 m6A modification, followed by LINC01273 decay in the presence of YTHDF2, a m6A 'reader'. And LINC01273 plays a key role in sorafenib resistant HCC cells.

Apoptosis regulatory protein Siva (SIVA1)

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				[124]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Target Regulation	Down regulation
In-vitro Model	HCT 8	Colon adenocarcinoma	Homo sapiens	CVCL_2478
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	HEK293T	Normal	Homo sapiens	CVCL_0063
	MC-38	Mouse colon adenocarcinoma	Mus musculus	CVCL_B288
In-vivo Model	For the tumor metastasis mouse model, 5-week-old C57BL/6 mice were randomly grouped and injected with 5 × 10⁵ Control or shFTO stable MC38 cells via tail vein. Drug administration was adopted after 48 h. Drug administration (intraperitoneally): DMSO, 5-FU (50 mg/kg every 2 days) or Rhein (10 mg/kg every 2 days). To detect lung metastasis, mice were killed 2 weeks after tumor cell injection. Lung tissues were harvested and fixed with 4% PFA for paraffin-embedded section and lung metastases were detected with Nikon microscopy. For tumor intraperitoneal mouse model, 2 × 10⁶ Dox-shCtrl, Dox-shFTO stable HCT8/5-FU cells were injected into 5-week-old male BALB/C nude mice. Drug administration was adopted after 48 h. Drug administration (intraperitoneally): DMSO, 5-FU (50 mg/kg every 2 days) or FB23-2 (10 mg/kg every 2 days). For tumor intraperitoneal mouse model, 5 × 10⁵ shCtrl, shFTO-1, shFTO-2 stable MC38 cells were injected into 5-week-old C57BL/6 mice. Drug administration was adopted after 48 h. Drug administration (intraperitoneally): DMSO, 5-FU (50 mg/kg every 2 days) or Rhein (10 mg/kg every 2 days).

Aryl hydrocarbon receptor (AHR)

Target Gene

Tislelizumab [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[104]
Responsed Disease	Glioblastoma		ICD-11: 2A00.00	Disease Info
In-vitro Model	U-87MG ATCC	Glioblastoma	Homo sapiens	CVCL_0022

CD70 antigen (CD70)

Target Gene

JNJ-74494550 [Phase 2]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[129]
Responsed Disease	Papillary thyroid cancer		ICD-11: 2D10.1	Disease Info
Target Regulation	Down regulation
In-vitro Model	Nthy-ori 3-1	Normal	Homo sapiens	CVCL_2659
	B-CPAP	Thyroid gland carcinoma	Homo sapiens	CVCL_0153
	K1	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_2537
	C-643	Thyroid gland anaplastic carcinoma	Homo sapiens	CVCL_5969
	BHT-101	Thyroid gland anaplastic carcinoma	Homo sapiens	CVCL_1085
	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
In-vivo Model	NCG mice (female, 4-5 weeks old, purchased from Jiangsu GemPharmatech) were acclimated for 1 week and were selected randomly to subcutaneously (s.c.) injected with 100 μl suspensions of 1 × 10⁶ thyroid cancer cell lines. All mice were housed in animal facility under specific pathogen-free conditions. After 7 day, 5 × 10⁶ huPBMCs were intravenously (i.v.) inoculated into mice. Mice were treated intravenously with anti-PD-1 mAb (nivolumab, 200 μg per injection), Combination (nivolumab + anti-CD70 mAb cusatuzumab, 200 μg per injection each), or PBS once a week. The treatment with M2-TAMs EVs or PBS continued in mice at 2ug EVs per injection at the tumor site twice a week [24]. The body weight of mice and the length (mm) and width (mm) of tumors were monitored every 3 or 4 days. Tumor volume (mm3) was calculated as Length × Width2 × 1/2. Tumor growth analyses were limited to 3 to 4 weeks because following this period mice started to show signs of xenograft-versus-host disease (xGVHD). Therefore, after 14 days or 21 days of PBMCs implantation, the mice were euthanized.

Circ_ASK1

Target Gene

Gefitinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[131]
Responsed Disease	Lung adenocarcinoma		ICD-11: 2C25.0	Disease Info
Target Regulation	Down regulation
Cell Process	Cell apoptosis
In-vitro Model	SPC-A1	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
	SK-LU-1	Lung adenocarcinoma	Homo sapiens	CVCL_0629
	NCI-H1993	Lung adenocarcinoma	Homo sapiens	CVCL_1512
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	HEK293T	Normal	Homo sapiens	CVCL_0063
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	16HBE14o-	Normal	Homo sapiens	CVCL_0112
In-vivo Model	Established a xenograft model in BALB/c nude mice by inoculating HCC827-GR cells transfected with the constructs for circASK1 silencing, ASK1-272a.a overexpression and ASK1-272a.a overexpression/circASK1 knockdown.
Response Summary	Increased YTHDF2-mediated endoribonucleolytic cleavage of m6A-modified Circ_ASK1 accounts for its downregulation in gefitinib-resistant cells. Either METTL3 silencing or YTHDF2 silencing suppressed the decay of circASK1 in HCC827-GR cells. This study provides a novel therapeutic target to overcome gefitinib resistance in LUAD patients.

Circ_RERE

Target Gene

ICG-001 [Investigative]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[135]
Responsed Disease	Osteoarthritis	ICD-11: FA05	Disease Info
Target Regulation	Down regulation

Complement C1q subcomponent subunit A (C1QA)

Target Gene

Rituximab [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[138]
Responsed Disease	Diffuse large B-cell lymphomas	ICD-11: 2A81	Disease Info
Target Regulation	Down regulation
In-vivo Model	Approximately 2 × 10⁶ Farage/R or Farage/S cells stably transfected with shNC, shC1qA or shMETTL3 were subcutaneously injected into the left flank of each mouse. When the tumor volume reached ~100 mm3, each mouse received an intraperitoneal injection of Rituximab (20 mg/kg) every 4 days for a total of 5 injections. The diameter of each tumor was examined every 4 days using a caliper, and tumor volume was calculated as follows: (length × width2)/2. At 28 days after xenograft, the mice were sacrificed and the tumors were weighed and collected.

CREB-binding protein (CREBBP)

Target Gene

PT2385 [Investigative]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene		[139]
Target Regulation	Up regulation

DNA replication licensing factor MCM7 (MCM2)

Target Gene

OSMI-1 [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[69]
Responsed Disease	Liver hepatocellular carcinoma		ICD-11: 2C12.02	Disease Info
Target Regulation	Up regulation
In-vitro Model	HepAD38	Hepatoblastoma	Homo sapiens	CVCL_M177
	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	HEK293	Normal	Homo sapiens	CVCL_0045
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	For the xenograft implantation model, 2 × 10⁶ MHCC-97H cells were subcutaneously injected into the flank of nude mice.

GTP cyclohydrolase 1 (GCH1)

Target Gene

Fluorene-9-bisphenol [Investigative]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene		[108]
Target Regulation	Up regulation

long intergenic non-protein coding RNA 115 (LINC00115)

Target Gene

Acetaminophen [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[154]
Responsed Disease	Triple-negative breast cancer	ICD-11: 2C6Z	Disease Info
Target Regulation	Down regulation

Mitogen-activated protein kinase 13 (MAPK13)

Target Gene

Rapamycin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[158]
Target Regulation	Down regulation
In-vitro Model	621-101	Lung lymphangioleiomyomatosis	Homo sapiens	CVCL_S879
	HEK293-EBNA	N.A.	Homo sapiens	CVCL_6974
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	UMB1949	Kidney angiomyolipoma	Homo sapiens	CVCL_C471

Peroxiredoxin-5, mitochondrial (PRDX5)

Target Gene

FB23-2 [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[162]
Target Regulation	Up regulation
In-vitro Model	HaCaT	Normal	Homo sapiens	CVCL_0038

Prolyl endopeptidase FAP (FAP)

Target Gene

VS-6063 [Phase 2]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[164]
Responsed Disease	Non-small cell lung cancer		ICD-11: 2C25.Y	Disease Info
In-vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	SK-MES-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_0630
	BEAS-2B	Normal	Homo sapiens	CVCL_0168
In-vivo Model	The Laboratory Animal Center of Soochow University provided female BALB/c nude mice (5 weeks old). Mice were kept under specific pathogen-free conditions. They were injected intravenously (i.v.) with FTO-overexpressing and control A549 cells (1.8 × 10⁶ cells/mouse) to establish the in vivo model of NSCLC metastasis, and were then gavaged with dimethyl sulfoxide (DMSO) (25 mg/kg, daily) or the FAK inhibitor defactinib (VS6063) (Cat#S7654, Selleck, USA) (25 mg/kg, daily) beginning in the fifth week after injection. The mice were euthanized eight weeks after being inoculated, and their lungs were taken out and preserved in Bouin's solution for macroscopic investigation of metastatic nodules. Hematoxylin and eosin (H&E) staining of lung tissues was used to look for micrometastatic foci.

Pseudorabies Virus (PRV)

Target Gene

3-deazidenosine [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[169]
Responsed Disease	Rabies		ICD-11: 1C82	Disease Info
Target Regulation	Up regulation
In-vitro Model	PK-15	N.A.	Sus scrofa	CVCL_2160

Unspecific Target Gene

Teniposide [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[189]
Responsed Disease	Hepatocellular carcinoma		ICD-11: 2C12.02	Disease Info
Pathway Response	Nucleotide excision repair			hsa03420
	mTOR signaling pathway			hsa04150
Cell Process	DNA repair
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
In-vivo Model	To establish a tumour model, C57BL/6 mice were intraperitoneal injected with 25 mg/kg diethylnitrosamine at 2 weeks of age.
Response Summary	The m6A model includes LRPPRC, YTHDF2, KIAA14219, and RBM15B, classified A-hepatocellular carcinoma patients into high/low-risk subtypes. The expression of Immunosuppressive cytokines DNMT1/EZH2 was up-regulated in A-hepatocellular carcinoma patients, and teniposide can be a potential therapeutic drug for A-hepatocellular carcinoma.

Click to View Potential Drug Response of This Regulator

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

RNA modification

m6A Target: Ubiquitin domain-containing protein TINC (TINCR)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT00017		Crosstalk Info
Epigenetic Regulator	tRNA (adenine(58)-N(1))-methyltransferase non-catalytic subunit TRM6 (TRMT6)
Regulated Target	TINCR ubiquitin domain containing (TINCR)
Crosstalk relationship	m1A → m6A
Crosstalk ID: M6ACROT00018		Crosstalk Info
Epigenetic Regulator	tRNA (adenine(58)-N(1))-methyltransferase catalytic subunit TRMT61A (TRMT61A)
Regulated Target	TINCR ubiquitin domain containing (TINCR)
Crosstalk relationship	m1A → m6A

m6A Target: Protein SON

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT00019		Crosstalk Info
Epigenetic Regulator	tRNA (adenine(58)-N(1))-methyltransferase non-catalytic subunit TRM6 (TRMT6)
Regulated Target	Protein SON
Crosstalk relationship	m1A → m6A
Crosstalk ID: M6ACROT00020		Crosstalk Info
Epigenetic Regulator	tRNA (adenine(58)-N(1))-methyltransferase catalytic subunit TRMT61A (TRMT61A)
Regulated Target	Protein SON
Crosstalk relationship	m1A → m6A

m6A Target: Circ_MATR3

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT00021		Crosstalk Info
Epigenetic Regulator	tRNA (adenine(58)-N(1))-methyltransferase non-catalytic subunit TRM6 (TRMT6)
Regulated Target	Circ_MATR3
Crosstalk relationship	m1A → m6A
Crosstalk ID: M6ACROT00022		Crosstalk Info
Epigenetic Regulator	tRNA (adenine(58)-N(1))-methyltransferase catalytic subunit TRMT61A (TRMT61A)
Regulated Target	Circ_MATR3
Crosstalk relationship	m1A → m6A

m6A Target: Circ_FAM20B

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT00023		Crosstalk Info
Epigenetic Regulator	tRNA (adenine(58)-N(1))-methyltransferase non-catalytic subunit TRM6 (TRMT6)
Regulated Target	Circ_FAM20B
Crosstalk relationship	m1A → m6A
Crosstalk ID: M6ACROT00024		Crosstalk Info
Epigenetic Regulator	tRNA (adenine(58)-N(1))-methyltransferase catalytic subunit TRMT61A (TRMT61A)
Regulated Target	Circ_FAM20B
Crosstalk relationship	m1A → m6A

m6A Target: Circ_SLC45A4

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT00025		Crosstalk Info
Epigenetic Regulator	tRNA (adenine(58)-N(1))-methyltransferase non-catalytic subunit TRM6 (TRMT6)
Regulated Target	Circ_SLC45A4
Crosstalk relationship	m1A → m6A
Crosstalk ID: M6ACROT00026		Crosstalk Info
Epigenetic Regulator	tRNA (adenine(58)-N(1))-methyltransferase catalytic subunit TRMT61A (TRMT61A)
Regulated Target	Circ_SLC45A4
Crosstalk relationship	m1A → m6A

m6A Target: Myc proto-oncogene protein (MYC)

Target Gene

In total 3 item(s) under this m6A target
Crosstalk ID: M6ACROT00028		Crosstalk Info
Epigenetic Regulator	tRNA methyltransferase 10 homolog A (TRMT10A)
Regulated Target	tRNA-Gln (anticodon TTG) 1-1 (TRQ-TTG1-1)
Crosstalk relationship	m1G → m6A
Drug	AVI-5126	Drug Info
Crosstalk ID: M6ACROT00030		Crosstalk Info
Epigenetic Regulator	tRNA methyltransferase 10 homolog A (TRMT10A)
Regulated Target	tRNA-Arg (anticodon CCG) 1-1 (TRR-CCG1-1)
Crosstalk relationship	m1G → m6A
Drug	AVI-5126	Drug Info
Crosstalk ID: M6ACROT00032		Crosstalk Info
Epigenetic Regulator	tRNA methyltransferase 10 homolog A (TRMT10A)
Regulated Target	tRNA-Thr (anticodon CGT) 1-1 (TRT-CGT1-1)
Crosstalk relationship	m1G → m6A
Drug	AVI-5126	Drug Info

m6A Target: Forkhead box protein D1 (FOXD1)

Target Gene

In total 3 item(s) under this m6A target
Crosstalk ID: M6ACROT00034		Crosstalk Info
Epigenetic Regulator	tRNA methyltransferase 10 homolog A (TRMT10A)
Regulated Target	tRNA-Gln (anticodon TTG) 1-1 (TRQ-TTG1-1)
Crosstalk relationship	m1G → m6A
Crosstalk ID: M6ACROT00036		Crosstalk Info
Epigenetic Regulator	tRNA methyltransferase 10 homolog A (TRMT10A)
Regulated Target	tRNA-Arg (anticodon CCG) 1-1 (TRR-CCG1-1)
Crosstalk relationship	m1G → m6A
Crosstalk ID: M6ACROT00038		Crosstalk Info
Epigenetic Regulator	tRNA methyltransferase 10 homolog A (TRMT10A)
Regulated Target	tRNA-Thr (anticodon CGT) 1-1 (TRT-CGT1-1)
Crosstalk relationship	m1G → m6A

m6A Target: Small ribosomal subunit protein mS38 (AURKAIP1)

Target Gene

In total 3 item(s) under this m6A target
Crosstalk ID: M6ACROT00040		Crosstalk Info
Epigenetic Regulator	tRNA methyltransferase 10 homolog A (TRMT10A)
Regulated Target	tRNA-Gln (anticodon TTG) 1-1 (TRQ-TTG1-1)
Crosstalk relationship	m1G → m6A
Crosstalk ID: M6ACROT00042		Crosstalk Info
Epigenetic Regulator	tRNA methyltransferase 10 homolog A (TRMT10A)
Regulated Target	tRNA-Arg (anticodon CCG) 1-1 (TRR-CCG1-1)
Crosstalk relationship	m1G → m6A
Crosstalk ID: M6ACROT00044		Crosstalk Info
Epigenetic Regulator	tRNA methyltransferase 10 homolog A (TRMT10A)
Regulated Target	tRNA-Thr (anticodon CGT) 1-1 (TRT-CGT1-1)
Crosstalk relationship	m1G → m6A

m6A Target: Transcription factor SOX-9 (SOX9)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT00068		Crosstalk Info
Epigenetic Regulator	5-methylcytosine rRNA methyltransferase NSUN4 (NSUN4)
Regulated Target	Transcription factor SOX-9 (SOX9)
Crosstalk relationship	m6A → m5C

m6A Target: Double-stranded RNA-specific editase 1 (ADARB1)

Target Gene

In total 27 item(s) under this m6A target
Crosstalk ID: M6ACROT00082		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	Filamin-A (FLNA)
Crosstalk relationship	m6A → A-to-I
Drug	PTI-125	Drug Info
Crosstalk ID: M6ACROT00084		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	Glutamate ionotropic receptor AMPA type subunit 2 (GRIA2)
Crosstalk relationship	m6A → A-to-I
Drug	E-2007	Drug Info
Crosstalk ID: M6ACROT00086		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	Cytoplasmic FMR1 interacting protein 2 (CYFIP2)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00090		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	Cell division cycle 14B (CDC14B)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00094		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	Zinc finger protein GLI1 (GLI1)
Crosstalk relationship	m6A → A-to-I
Drug	PMID26666870-Compound-16	Drug Info
Crosstalk ID: M6ACROT00096		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	microRNA 16-1 (MIR16-1)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00099		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	microRNA 122 (MIR122)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00101		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	microRNA 214 (MIR214)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00103		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	Oligophrenin 1 (OPHN1)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00105		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	microRNA 21 (MIR21)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00107		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	microRNA 221 (MIR221)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00109		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	microRNA 222 (MIR222)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00119		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	Podocalyxin like (PODXL)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00122		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	Insulin-like growth factor-binding protein 7 (IGFBP7)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00134		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	Thiol methyltransferase 1A (TMT1A)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00140		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	Pellino E3 ubiquitin protein ligase 1 (PELI1)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00142		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	Protein sprouty homolog 2 (SPRY2)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00145		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	Heterogeneous nuclear ribonucleoprotein L like (HNRNPLL)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00148		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	microRNA 142 (MIR142)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00151		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	Protein SON
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00153		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	Glutamate ionotropic receptor kainate type subunit 2 (GRIK2)
Crosstalk relationship	m6A → A-to-I
Drug	2,4-epi-neodysiherbaine	Drug Info
Crosstalk ID: M6ACROT00163		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	Cytochrome P450 2B6 (CYP2B6)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00165		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	Cytochrome P450 2C8 (CYP2C8)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00167		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	Hepatocyte nuclear factor 4 alpha (HNF4A)
Crosstalk relationship	m6A → A-to-I
Drug	BI6015	Drug Info
Crosstalk ID: M6ACROT00170		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	CXADR cell adhesion molecule (CXADR)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00185		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	Farnesyltransferase, CAAX box, subunit alpha (FNTA)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00202		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	Nuclear receptor subfamily 1 group I member 2 (NR1I2)
Crosstalk relationship	m6A → A-to-I
Drug	Pregnenolone-16alpha-carbonitrile	Drug Info

m6A Target: Runt-related transcription factor 1 (RUNX1)

Target Gene

In total 3 item(s) under this m6A target
Crosstalk ID: M6ACROT00419		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	MicroRNA 21 (MIR21)
Crosstalk relationship	A-to-I → m6A
Crosstalk ID: M6ACROT00420		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	MicroRNA 21 (MIR21)
Crosstalk relationship	A-to-I → m6A
Crosstalk ID: M6ACROT00514		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	hsa-mir-18a
Crosstalk relationship	A-to-I → m6A

m6A Target: X inactive specific transcript (XIST)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT00423		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	MicroRNA 21 (MIR21)
Crosstalk relationship	m6A → A-to-I
Crosstalk ID: M6ACROT00424		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	MicroRNA 21 (MIR21)
Crosstalk relationship	m6A → A-to-I

m6A Target: Cellular tumor antigen p53 (TP53/p53)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT00433		Crosstalk Info
Epigenetic Regulator	Methyltransferase-like protein 1 (METTL1)
Regulated Target	MicroRNA 125a (MIR125A)
Crosstalk relationship	m7G → m6A
Crosstalk ID: M6ACROT00438		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	MicroRNA 214 (MIR214)
Crosstalk relationship	A-to-I → m6A

m6A Target: Epidermal growth factor receptor (EGFR)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT00442		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	MicroRNA 214 (MIR214)
Crosstalk relationship	A-to-I → m6A

m6A Target: Pvt1 oncogene (PVT1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT00451		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	MicroRNA 214 (MIR214)
Crosstalk relationship	m6A → A-to-I

m6A Target: Zinc finger protein SNAI1 (SNAI1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT00485		Crosstalk Info
Epigenetic Regulator	Fat mass and obesity-associated protein (FTO)
Regulated Target	hsa-mir-22
Crosstalk relationship	m6Am → m6A

m6A Target: Cyclic-AMP-dependent transcription factor ATF-3 (ATF3)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT00507		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	MicroRNA 222 (MIR222)
Crosstalk relationship	A-to-I → m6A
Crosstalk ID: M6ACROT00508		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	MicroRNA 222 (MIR222)
Crosstalk relationship	A-to-I → m6A

m6A Target: Forkhead box protein O3 (FOXO3)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT00520		Crosstalk Info
Epigenetic Regulator	Double-stranded RNA-specific editase 1 (ADARB1)
Regulated Target	MicroRNA 221 (MIR221)
Crosstalk relationship	A-to-I → m6A
Crosstalk ID: M6ACROT00555		Crosstalk Info
Epigenetic Regulator	Y-box-binding protein 1 (YBX1)
Regulated Target	Growth arrest specific 5 (GAS5)
Crosstalk relationship	m5C → m6A

m6A Target: Mothers against decapentaplegic homolog 4 (SMAD4)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT00550		Crosstalk Info
Epigenetic Regulator	Interferon-inducible protein 4 (ADAR1)
Regulated Target	MicroRNA 210 (MIR210)
Crosstalk relationship	A-to-I → m6A

DNA modification

m6A Target: Methylcytosine dioxygenase TET1 (TET1)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT02011		Crosstalk Info
Epigenetic Regulator	Methylcytosine dioxygenase TET1 (TET1)
Regulated Target	Methyltransferase-like protein 3 (METTL3)
Crosstalk relationship	m6A → DNA modification
Crosstalk ID: M6ACROT02095		Crosstalk Info
Epigenetic Regulator	Methylcytosine dioxygenase TET1 (TET1)
Regulated Target	Signal transducer and activator of transcription 3 (STAT3)
Crosstalk relationship	m6A → DNA modification
Disease	Inflammatory pain	Disease Info

m6A Target: Semaphorin-3F (SEMA3F)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02018		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	Semaphorin-3F (SEMA3F)
Crosstalk relationship	m6A → DNA modification
Disease	Prostate cancer	Disease Info
Drug	Docetaxel	Drug Info

m6A Target: Peroxisome proliferator-activated receptor alpha (PPARalpha/PPARA)

Target Gene

In total 3 item(s) under this m6A target
Crosstalk ID: M6ACROT02022		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	FTO alpha-ketoglutarate dependent dioxygenase (FTO)
Crosstalk relationship	DNA modification → m6A
Disease	Renal ischemia-reperfusion injury	Disease Info
Drug	5-azacytidine	Drug Info
Crosstalk ID: M6ACROT02023		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	FTO alpha-ketoglutarate dependent dioxygenase (FTO)
Crosstalk relationship	DNA modification → m6A
Disease	Renal ischemia-reperfusion injury	Disease Info
Drug	5-azacytidine	Drug Info
Crosstalk ID: M6ACROT02024		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	FTO alpha-ketoglutarate dependent dioxygenase (FTO)
Crosstalk relationship	DNA modification → m6A
Disease	Renal ischemia-reperfusion injury	Disease Info
Drug	5-azacytidine	Drug Info

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

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02026		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target	Transcription factor E4F1 (E4F1)
Crosstalk relationship	m6A → DNA modification
Disease	Intervertebral disc degeneration	Disease Info

m6A Target: Transcription factor SOX-2 (SOX2)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02037		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	RNA demethylase ALKBH5 (ALKBH5)
Crosstalk relationship	DNA modification → m6A
Disease	Lung cancer	Disease Info

m6A Target: Mothers against decapentaplegic homolog 7 (SMAD7)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02038		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	RNA demethylase ALKBH5 (ALKBH5)
Crosstalk relationship	DNA modification → m6A
Disease	Lung cancer	Disease Info

m6A Target: Myc proto-oncogene protein (MYC)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02039		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	RNA demethylase ALKBH5 (ALKBH5)
Crosstalk relationship	DNA modification → m6A
Disease	Lung cancer	Disease Info

m6A Target: Cysteine methyltransferase DNMT3A (DNMT3A)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02071		Crosstalk Info
Epigenetic Regulator	Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target	Dachshund family transcription factor 1 (DACH1)
Crosstalk relationship	m6A → DNA modification
Disease	Chronic obstructive pulmonary disease	Disease Info

m6A Target: 6-phosphogluconate dehydrogenase, decarboxylating (6PGD/PGD)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02136		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	RNA demethylase ALKBH5 (ALKBH5)
Crosstalk relationship	DNA modification → m6A
Disease	Lung cancer	Disease Info

m6A Target: Protein FAM83D (FAM83D)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02137		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	RNA demethylase ALKBH5 (ALKBH5)
Crosstalk relationship	DNA modification → m6A
Disease	Lung cancer	Disease Info

m6A Target: Transforming growth factor beta-1 proprotein (TGFB1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02138		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	RNA demethylase ALKBH5 (ALKBH5)
Crosstalk relationship	DNA modification → m6A
Disease	Lung cancer	Disease Info

m6A Target: Mothers against decapentaplegic homolog 2 (SMAD2)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02139		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	RNA demethylase ALKBH5 (ALKBH5)
Crosstalk relationship	DNA modification → m6A
Disease	Lung cancer	Disease Info

m6A Target: Mothers against decapentaplegic homolog 3 (SMAD3)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT02140		Crosstalk Info
Epigenetic Regulator	DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target	RNA demethylase ALKBH5 (ALKBH5)
Crosstalk relationship	DNA modification → m6A
Disease	Lung cancer	Disease Info

Histone modification

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

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03006		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 4A (KDM4A)
Regulated Target	Histone H3 lysine 9 trimethylation (H3K9me3)
Crosstalk relationship	Histone modification → m6A
Disease	Intervertebral disc degeneration	Disease Info

m6A Target: Lysine-specific demethylase 6B (KDM6B)

Target Gene

In total 3 item(s) under this m6A target
Crosstalk ID: M6ACROT03014		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 6B (KDM6B)
Regulated Target	Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship	m6A → Histone modification
Disease	Inflammatory response	Disease Info
Crosstalk ID: M6ACROT03240		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 6B (KDM6B)
Regulated Target	Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship	m6A → Histone modification
Crosstalk ID: M6ACROT05995		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 6B (KDM6B)
Regulated Target	Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship	m6A → Histone modification
Disease	Inflammatory response	Disease Info

m6A Target: Transcription factor SOX-4 (SOX4)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03037		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5C (KDM5C)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Period circadian protein homolog 1 (PER1)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03047		Crosstalk Info
Epigenetic Regulator	Lactate dehydrogenase A (LDHA)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Melanoma of uvea	Disease Info
Crosstalk ID: M6ACROT03048		Crosstalk Info
Epigenetic Regulator	L-lactate dehydrogenase B chain (LDHB)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Melanoma of uvea	Disease Info

m6A Target: Cellular tumor antigen p53 (TP53/p53)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03049		Crosstalk Info
Epigenetic Regulator	Lactate dehydrogenase A (LDHA)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Melanoma of uvea	Disease Info
Crosstalk ID: M6ACROT03050		Crosstalk Info
Epigenetic Regulator	L-lactate dehydrogenase B chain (LDHB)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Melanoma of uvea	Disease Info

m6A Target: MOB kinase activator 3B (MOB3B)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03073		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5A (KDM5A)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Prostate cancer	Disease Info

m6A Target: Histone-lysine N-methyltransferase EZH2 (EZH2)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03082		Crosstalk Info
Epigenetic Regulator	Histone-lysine N-methyltransferase EZH2 (EZH2)
Regulated Target	Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship	m6A → Histone modification
Disease	Endometriosis	Disease Info

m6A Target: Histone deacetylase 4 (HDAC4)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03083		Crosstalk Info
Epigenetic Regulator	Histone deacetylase 4 (HDAC4)
Regulated Target	Hypoxia-inducible factor 1-alpha (HIF-1-Alpha/HIF1A)
Crosstalk relationship	m6A → Histone modification
Disease	Pancreatic cancer	Disease Info

m6A Target: Potassium channel subfamily K member 6 (KCNK6)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03085		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Cyclin-dependent kinase 2 (CDK2)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03087		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Diabetic retinopathy	Disease Info
Drug	FB23-2	Drug Info

m6A Target: Histone acetyltransferase KAT2A (KAT2A)

Target Gene

In total 4 item(s) under this m6A target
Crosstalk ID: M6ACROT03089		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase KAT2A (KAT2A)
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	m6A → Histone modification
Disease	Diabetic cardiomyopathy	Disease Info
Crosstalk ID: M6ACROT03091		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase KAT2A (KAT2A)
Regulated Target	Histone H3 lysine 9 acetylation (H3K9Ac)
Crosstalk relationship	m6A → Histone modification
Disease	Diabetic cardiomyopathy	Disease Info
Crosstalk ID: M6ACROT05845		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase KAT2A (KAT2A)
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	m6A → Histone modification
Disease	Diabetic cardiomyopathy	Disease Info
Crosstalk ID: M6ACROT05847		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase KAT2A (KAT2A)
Regulated Target	Histone H3 lysine 9 acetylation (H3K9ac)
Crosstalk relationship	m6A → Histone modification
Disease	Diabetic cardiomyopathy	Disease Info

m6A Target: long intergenic non-protein coding RNA 115 (LINC00115)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03105		Crosstalk Info
Epigenetic Regulator	Histone-lysine N-methyltransferase SETDB1 (SETDB1)
Regulated Target	Polo like kinase 3 (PLK3)
Crosstalk relationship	Histone modification → m6A
Disease	Triple-negative breast cancer	Disease Info
Drug	Acetaminophen	Drug Info

m6A Target: NACHT, LRR and PYD domains-containing protein 3 (NLRP3)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03108		Crosstalk Info
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Lung cancer	Disease Info
Drug	Gefitinib	Drug Info
Crosstalk ID: M6ACROT03110		Crosstalk Info
Regulated Target	Histone H3 lysine 4 monomethylation (H3K4me1)
Crosstalk relationship	Histone modification → m6A
Disease	Lung cancer	Disease Info
Drug	Gefitinib	Drug Info

m6A Target: Serine/threonine-protein kinase PAK 6 (PAK5)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03118		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Cervical cancer	Disease Info
Crosstalk ID: M6ACROT03120		Crosstalk Info
Epigenetic Regulator	WD repeat-containing protein 5 (WDR5)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Cervical cancer	Disease Info

m6A Target: ETS translocation variant 5 (ETV5)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03122		Crosstalk Info
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info
Crosstalk ID: M6ACROT03123		Crosstalk Info
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info

m6A Target: 5-hydroxytryptamine receptor 3A (HTR3A)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03130		Crosstalk Info
Epigenetic Regulator	Histone deacetylase 11 (HDAC11)
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Neuropathic pain	Disease Info

m6A Target: Transcriptional coactivator YAP1 (YAP1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03140		Crosstalk Info
Epigenetic Regulator	Lysine-specific histone demethylase 1A (KDM1A)
Regulated Target	Histone H3 lysine 4 dimethylation (H3K4me2)
Crosstalk relationship	Histone modification → m6A
Disease	Triple-negative breast cancer	Disease Info

m6A Target: Cysteine protease ATG4A (ATG4A)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03161		Crosstalk Info
Epigenetic Regulator	Histone-lysine N-methyltransferase 2A (KMT2A)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Intervertebral disc degeneration	Disease Info

m6A Target: Circ_SLC9A6

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03164		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase KAT8 (KAT8)
Regulated Target	Histone H4 lysine 16 acetylation (H4K16ac)
Crosstalk relationship	m6A → Histone modification
Disease	Nonalcoholic fatty liver disease	Disease Info

m6A Target: Thioredoxin domain-containing protein 5 (TXNDC5)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03171		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Cervical cancer	Disease Info
Crosstalk ID: M6ACROT03172		Crosstalk Info
Epigenetic Regulator	WD repeat-containing protein 5 (WDR5)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Cervical cancer	Disease Info

m6A Target: Methylcytosine dioxygenase TET1 (TET1)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03184		Crosstalk Info
Epigenetic Regulator	Methylcytosine dioxygenase TET1 (TET1)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Crosstalk ID: M6ACROT03185		Crosstalk Info
Epigenetic Regulator	Methylcytosine dioxygenase TET1 (TET1)
Regulated Target	Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship	Histone modification → m6A

m6A Target: testis expressed 41 (TEX41)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03197		Crosstalk Info
Epigenetic Regulator	Polycomb protein SUZ12 (SUZ12)
Regulated Target	Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship	m6A → Histone modification
Disease	Renal cell carcinoma	Disease Info

m6A Target: Taurine up-regulated 1 protein (TUG1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03203		Crosstalk Info
Epigenetic Regulator	Histone-lysine N-methyltransferase EHMT2 (EHMT2)
Regulated Target	Histone H3 lysine 9 dimethylation (H3K9me2)
Crosstalk relationship	m6A → Histone modification
Disease	Acute myeloid leukaemia	Disease Info
Drug	Adriamycin	Drug Info

m6A Target: Integrin beta-1 (ITGB1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03215		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase type B catalytic subunit (HAT1)
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Diabetic retinopathy	Disease Info

m6A Target: Tripartite motif-containing protein 72 (TRIM72)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03217		Crosstalk Info
Epigenetic Regulator	Histone-lysine N-methyltransferase 2A (KMT2A)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Preeclampsia	Disease Info
Drug	Actinomycin D	Drug Info

m6A Target: CREB-binding protein (CREBBP)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03219		Crosstalk Info
Epigenetic Regulator	CREB-binding protein (CREBBP)
Crosstalk relationship	m6A → Histone modification
Drug	BHBA	Drug Info

m6A Target: Mutated in multiple advanced cancers 1 (PTEN)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03221		Crosstalk Info
Epigenetic Regulator	Histone-lysine N-methyltransferase EZH2 (EZH2)
Regulated Target	Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship	Histone modification → m6A
Disease	Brain cancer	Disease Info

m6A Target: Histone-lysine N-methyltransferase EHMT2 (G9a)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03232		Crosstalk Info
Epigenetic Regulator	Histone-lysine N-methyltransferase EHMT2 (EHMT2)
Regulated Target	Histone H3 lysine 9 dimethylation (H3K9me2)
Crosstalk relationship	m6A → Histone modification
Disease	Neuropathic pain	Disease Info

m6A Target: Forkhead box protein O3 (FOXO3)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03238		Crosstalk Info
Epigenetic Regulator	CREB-binding protein (CREBBP)
Crosstalk relationship	m6A → Histone modification
Disease	Intervertebral disc degeneration	Disease Info

m6A Target: X inactive specific transcript (XIST)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03289		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5C (KDM5C)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info
Crosstalk ID: M6ACROT03333		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Transcription factor ISGF-3 components p91/p84 (Stat1)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03290		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5C (KDM5C)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info
Crosstalk ID: M6ACROT03346		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Interferon regulatory factor 1 (Irf1)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03291		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5C (KDM5C)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info
Crosstalk ID: M6ACROT03347		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Arrestin domain-containing protein 4 (ARRDC4)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03292		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5C (KDM5C)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info
Crosstalk ID: M6ACROT03348		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Thrombospondin-1 (THBS1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03327		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5A (KDM5A)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Prostate cancer	Disease Info

m6A Target: RAC-alpha serine/threonine-protein kinase (AKT1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03328		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5A (KDM5A)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Prostate cancer	Disease Info

m6A Target: Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03329		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5A (KDM5A)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Prostate cancer	Disease Info

m6A Target: Homeobox protein Nkx-3.1 (NKX3-1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03330		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5A (KDM5A)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Prostate cancer	Disease Info

m6A Target: Ubiquitin carboxyl-terminal hydrolase 4 (USP4)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03331		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5A (KDM5A)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Prostate cancer	Disease Info

m6A Target: ELAV-like protein 1 (HuR/ELAVL1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03332		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5A (KDM5A)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Prostate cancer	Disease Info

m6A Target: Cyclic AMP-dependent transcription factor ATF-4 (ATF4)

Target Gene

In total 6 item(s) under this m6A target
Crosstalk ID: M6ACROT03334		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info
Drug	Rapamycin	Drug Info
Crosstalk ID: M6ACROT03335		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info
Drug	GLS-IN-968	Drug Info
Crosstalk ID: M6ACROT03336		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info
Drug	CB-839	Drug Info
Crosstalk ID: M6ACROT03337		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info
Drug	Meclofenamate sodium	Drug Info
Crosstalk ID: M6ACROT03338		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info
Drug	Chloroquine	Drug Info
Crosstalk ID: M6ACROT03339		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info
Drug	Asparagine inhibitor	Drug Info

m6A Target: Serine/threonine-protein kinase mTOR (MTOR)

Target Gene

In total 6 item(s) under this m6A target
Crosstalk ID: M6ACROT03340		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info
Drug	Rapamycin	Drug Info
Crosstalk ID: M6ACROT03341		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info
Drug	GLS-IN-968	Drug Info
Crosstalk ID: M6ACROT03342		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info
Drug	CB-839	Drug Info
Crosstalk ID: M6ACROT03343		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info
Drug	Meclofenamate sodium	Drug Info
Crosstalk ID: M6ACROT03344		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info
Drug	Chloroquine	Drug Info
Crosstalk ID: M6ACROT03345		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info
Drug	Asparagine inhibitor	Drug Info

m6A Target: Protein yippee-like 5 (YPEL5)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03349		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Circ_AFF2

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03350		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Apoptosis regulatory protein Siva (SIVA1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03351		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info
Drug	Fluorouracil	Drug Info

m6A Target: Ras-related protein Rab-5A (RAB5A)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03352		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship	Histone modification → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Growth arrest specific 5 (GAS5)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03405		Crosstalk Info
Epigenetic Regulator	Histone acetyltransferase p300 (P300)
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Cervical cancer	Disease Info
Crosstalk ID: M6ACROT03408		Crosstalk Info
Epigenetic Regulator	WD repeat-containing protein 5 (WDR5)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Cervical cancer	Disease Info

m6A Target: Epidermal growth factor receptor (EGFR)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03409		Crosstalk Info
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info
Crosstalk ID: M6ACROT03420		Crosstalk Info
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info

m6A Target: POU domain, class 5, transcription factor 1 (POU5F1)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03410		Crosstalk Info
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info
Crosstalk ID: M6ACROT03421		Crosstalk Info
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info

m6A Target: Interleukin-11 (IL11)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03411		Crosstalk Info
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info
Drug	PT2385*	Drug Info
Crosstalk ID: M6ACROT03422		Crosstalk Info
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info
Drug	PT2385*	Drug Info

m6A Target: Glia-derived nexin (SERPINE2)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03412		Crosstalk Info
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info
Drug	PT2385*	Drug Info
Crosstalk ID: M6ACROT03423		Crosstalk Info
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info
Drug	PT2385*	Drug Info

m6A Target: Splicing factor 3A subunit 3 (SF3A3)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03413		Crosstalk Info
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info
Crosstalk ID: M6ACROT03424		Crosstalk Info
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info

m6A Target: Tyrosine-protein kinase Fyn (FYN)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03414		Crosstalk Info
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info
Crosstalk ID: M6ACROT03425		Crosstalk Info
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info

m6A Target: Proliferation-associated protein 2G4 (PA2G4)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03415		Crosstalk Info
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info
Crosstalk ID: M6ACROT03426		Crosstalk Info
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info

m6A Target: Long intergenic non-protein coding RNA 1273 (LINC01273)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03416		Crosstalk Info
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info
Drug	Sorafenib	Drug Info
Crosstalk ID: M6ACROT03427		Crosstalk Info
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info
Drug	Sorafenib	Drug Info

m6A Target: Glucose transporter type 1 (GLUT1)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03417		Crosstalk Info
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info
Crosstalk ID: M6ACROT03428		Crosstalk Info
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info

m6A Target: Pyruvate kinase PKM (PKM2/PKM)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT03418		Crosstalk Info
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info
Crosstalk ID: M6ACROT03429		Crosstalk Info
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info

m6A Target: Myc proto-oncogene protein (MYC)

Target Gene

In total 3 item(s) under this m6A target
Crosstalk ID: M6ACROT03419		Crosstalk Info
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info
Crosstalk ID: M6ACROT03430		Crosstalk Info
Regulated Target	Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship	Histone modification → m6A
Disease	Liver cancer	Disease Info
Crosstalk ID: M6ACROT03539		Crosstalk Info
Epigenetic Regulator	Histone-lysine N-methyltransferase EZH2 (EZH2)
Regulated Target	Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship	Histone modification → m6A
Disease	Brain cancer	Disease Info

m6A Target: UBX domain-containing protein 1 (UBXN1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03540		Crosstalk Info
Epigenetic Regulator	Histone-lysine N-methyltransferase EZH2 (EZH2)
Regulated Target	Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship	Histone modification → m6A
Disease	Brain cancer	Disease Info

m6A Target: Nuclear factor NF-kappa-B p105 subunit (NF-Kappa-B/NFKB1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT03541		Crosstalk Info
Epigenetic Regulator	Histone-lysine N-methyltransferase EZH2 (EZH2)
Regulated Target	Histone H3 lysine 27 trimethylation (H3K27me3)
Crosstalk relationship	Histone modification → m6A
Disease	Brain cancer	Disease Info

m6A Target: Long intergenic non-protein coding RNA 657 (NORAD)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05974		Crosstalk Info
Epigenetic Regulator	Lysine-specific demethylase 5A (KDM5A)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Disease	Intervertebral disc degeneration	Disease Info

Non-coding RNA

m6A Target: Epidermal growth factor receptor (EGFR)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05037		Crosstalk Info
Epigenetic Regulator	MicroRNA 145 (MIR145)
Regulated Target	YTH domain-containing family protein 2 (YTHDF2)
Crosstalk relationship	ncRNA → m6A
Disease	Liver cancer	Disease Info

m6A Target: POU domain, class 5, transcription factor 1 (POU5F1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05038		Crosstalk Info
Epigenetic Regulator	MicroRNA 145 (MIR145)
Regulated Target	YTH domain-containing family protein 2 (YTHDF2)
Crosstalk relationship	ncRNA → m6A
Disease	Liver cancer	Disease Info

m6A Target: Interleukin-11 (IL11)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05039		Crosstalk Info
Epigenetic Regulator	MicroRNA 145 (MIR145)
Regulated Target	YTH domain-containing family protein 2 (YTHDF2)
Crosstalk relationship	ncRNA → m6A
Disease	Liver cancer	Disease Info

m6A Target: Glia-derived nexin (SERPINE2)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05040		Crosstalk Info
Epigenetic Regulator	MicroRNA 145 (MIR145)
Regulated Target	YTH domain-containing family protein 2 (YTHDF2)
Crosstalk relationship	ncRNA → m6A
Disease	Liver cancer	Disease Info

m6A Target: Splicing factor 3A subunit 3 (SF3A3)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05041		Crosstalk Info
Epigenetic Regulator	MicroRNA 145 (MIR145)
Regulated Target	YTH domain-containing family protein 2 (YTHDF2)
Crosstalk relationship	ncRNA → m6A
Disease	Liver cancer	Disease Info

m6A Target: Tyrosine-protein kinase Fyn (FYN)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05042		Crosstalk Info
Epigenetic Regulator	MicroRNA 145 (MIR145)
Regulated Target	YTH domain-containing family protein 2 (YTHDF2)
Crosstalk relationship	ncRNA → m6A
Disease	Liver cancer	Disease Info

m6A Target: Proliferation-associated protein 2G4 (PA2G4)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05043		Crosstalk Info
Epigenetic Regulator	MicroRNA 145 (MIR145)
Regulated Target	YTH domain-containing family protein 2 (YTHDF2)
Crosstalk relationship	ncRNA → m6A
Disease	Liver cancer	Disease Info

m6A Target: Long intergenic non-protein coding RNA 1273 (LINC01273)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT05044		Crosstalk Info
Epigenetic Regulator	MicroRNA 145 (MIR145)
Regulated Target	YTH domain-containing family protein 2 (YTHDF2)
Crosstalk relationship	ncRNA → m6A
Disease	Liver cancer	Disease Info
Crosstalk ID: M6ACROT05612		Crosstalk Info
Epigenetic Regulator	Long intergenic non-protein coding RNA 1273 (LINC01273)
Regulated Target	hsa-miR-600
Crosstalk relationship	m6A → ncRNA
Disease	Liver cancer	Disease Info
Drug	Sorafenib	Drug Info

m6A Target: Glucose transporter type 1 (SLC2A1)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT05045		Crosstalk Info
Epigenetic Regulator	MicroRNA 145 (MIR145)
Regulated Target	YTH domain-containing family protein 2 (YTHDF2)
Crosstalk relationship	ncRNA → m6A
Disease	Liver cancer	Disease Info
Crosstalk ID: M6ACROT05317		Crosstalk Info
Epigenetic Regulator	FTO intronic transcript 1 (FTO-IT1)
Regulated Target	FTO alpha-ketoglutarate dependent dioxygenase (FTO)
Crosstalk relationship	ncRNA → m6A
Disease	Liver cancer	Disease Info

m6A Target: Pyruvate kinase PKM (PKM2/PKM)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT05046		Crosstalk Info
Epigenetic Regulator	MicroRNA 145 (MIR145)
Regulated Target	YTH domain-containing family protein 2 (YTHDF2)
Crosstalk relationship	ncRNA → m6A
Disease	Liver cancer	Disease Info
Crosstalk ID: M6ACROT05316		Crosstalk Info
Epigenetic Regulator	FTO intronic transcript 1 (FTO-IT1)
Regulated Target	FTO alpha-ketoglutarate dependent dioxygenase (FTO)
Crosstalk relationship	ncRNA → m6A
Disease	Liver cancer	Disease Info

m6A Target: Myc proto-oncogene protein (MYC)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05047		Crosstalk Info
Epigenetic Regulator	MicroRNA 145 (MIR145)
Regulated Target	YTH domain-containing family protein 2 (YTHDF2)
Crosstalk relationship	ncRNA → m6A
Disease	Liver cancer	Disease Info

m6A Target: Growth arrest specific 5 (GAS5)

Target Gene

In total 3 item(s) under this m6A target
Crosstalk ID: M6ACROT05050		Crosstalk Info
Epigenetic Regulator	GAS5 antisense RNA 1 (GAS5-AS1)
Regulated Target	RNA demethylase ALKBH5 (ALKBH5)
Crosstalk relationship	ncRNA → m6A
Disease	Cervical cancer	Disease Info
Crosstalk ID: M6ACROT05398		Crosstalk Info
Epigenetic Regulator	Growth arrest specific 5 (GAS5)
Regulated Target	GAS5 antisense RNA 1 (GAS5-AS1)
Crosstalk relationship	m6A → ncRNA
Disease	Cervical cancer	Disease Info
Crosstalk ID: M6ACROT05718		Crosstalk Info
Epigenetic Regulator	Growth arrest specific 5 (GAS5)
Regulated Target	Dynamin-1-like protein (DRP1)
Crosstalk relationship	m6A → ncRNA
Disease	Vascular disorders of the liver	Disease Info

m6A Target: Fibulin-1 (FBLN1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05061		Crosstalk Info
Epigenetic Regulator	hsa-miR-615-3p
Regulated Target	YTH domain-containing family protein 2 (YTHDF2)
Crosstalk relationship	ncRNA → m6A
Disease	Maxillofacial bone defect is a critical obstacle for maxillofacial tumors and periodontal diseases.	Disease Info

m6A Target: Transcription factor E2F6 (E2F6)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05068		Crosstalk Info
Epigenetic Regulator	Read-through Circular RNA E2F
Regulated Target	Insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2)
Crosstalk relationship	ncRNA → m6A
Disease	Liver cancer	Disease Info

m6A Target: Transcription factor E2F3 (E2F3)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05069		Crosstalk Info
Epigenetic Regulator	Read-through Circular RNA E2F
Regulated Target	Insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2)
Crosstalk relationship	ncRNA → m6A
Disease	Liver cancer	Disease Info

m6A Target: Ubiquitin carboxyl-terminal hydrolase 38 (USP38)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05175		Crosstalk Info
Epigenetic Regulator	hsa-miR-3165
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Bladder cancer	Disease Info

m6A Target: Tyrosine-protein kinase JAK1 (JAK1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05209		Crosstalk Info
Epigenetic Regulator	Long intergenic non-protein coding RNA 659 (LINC00659)
Regulated Target	RNA demethylase ALKBH5 (ALKBH5)
Crosstalk relationship	ncRNA → m6A
Disease	Gastric cancer	Disease Info

m6A Target: Metalloreductase STEAP3 (STEAP3)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05211		Crosstalk Info
Epigenetic Regulator	STEAP3 antisense RNA 1 (STEAP3-AS1)
Regulated Target	YTH domain-containing family protein 2 (YTHDF2)
Crosstalk relationship	ncRNA → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: NACHT, LRR and PYD domains-containing protein 3 (NLRP3)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05224		Crosstalk Info
Epigenetic Regulator	MIR570 host gene (MIR570HG)
Regulated Target	Methyltransferase-like protein 3 (METTL3)
Crosstalk relationship	ncRNA → m6A
Disease	Lung cancer	Disease Info
Drug	Gefitinib	Drug Info

m6A Target: Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05278		Crosstalk Info
Epigenetic Regulator	hsa-miR-6125
Regulated Target	YTH domain-containing family protein 2 (YTHDF2)
Crosstalk relationship	ncRNA → m6A
Disease	Colorectal cancer	Disease Info

m6A Target: Heme oxygenase 1 (HMOX1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05280		Crosstalk Info
Epigenetic Regulator	hsa-miR-340-3p
Regulated Target	Methyltransferase-like protein 3 (METTL3)
Crosstalk relationship	ncRNA → m6A
Disease	Diseases of the female genital system	Disease Info

m6A Target: Mutated in multiple advanced cancers 1 (PTEN)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05288		Crosstalk Info
Epigenetic Regulator	Long intergenic non-protein coding RNA 470 (LINC00470)
Regulated Target	Methyltransferase-like protein 3 (METTL3)
Crosstalk relationship	ncRNA → m6A
Disease	Gastric cancer	Disease Info

m6A Target: MOB kinase activator 3B (MOB3B)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05297		Crosstalk Info
Epigenetic Regulator	hsa-miR-495
Regulated Target	YTH domain-containing family protein 2 (YTHDF2)
Crosstalk relationship	ncRNA → m6A
Disease	Prostate cancer	Disease Info

m6A Target: Bcl-2-modifying factor (BMF)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05308		Crosstalk Info
Epigenetic Regulator	MicroRNA 145 (MIR145)
Regulated Target	YTH domain-containing family protein 2 (YTHDF2)
Crosstalk relationship	ncRNA → m6A
Disease	Ovarian cancer	Disease Info

m6A Target: Cystathionine beta-synthase (CBS)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05350		Crosstalk Info
Epigenetic Regulator	CBS mRNA stabilizing lncRNA (CBSLR)
Regulated Target	YTH domain-containing family protein 2 (YTHDF2)
Crosstalk relationship	ncRNA → m6A
Disease	Gastric cancer	Disease Info

m6A Target: Transcription factor SOX-9 (SOX9)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05371		Crosstalk Info
Epigenetic Regulator	Circ_FTO
Regulated Target	Methyltransferase-like protein 14 (METTL14)
Crosstalk relationship	ncRNA → m6A
Disease	Rheumatoid arthritis	Disease Info

m6A Target: Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05373		Crosstalk Info
Epigenetic Regulator	Myocardial infarction associated transcript (MIAT)
Regulated Target	YTH domain-containing family protein 2 (YTHDF2)
Crosstalk relationship	ncRNA → m6A
Disease	Heart failure	Disease Info

m6A Target: Long intergenic non-protein coding RNA 470 (LINC00470)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05401		Crosstalk Info
Epigenetic Regulator	Long intergenic non-protein coding RNA 470 (LINC00470)
Regulated Target	Mutated in multiple advanced cancers 1 (PTEN)
Crosstalk relationship	m6A → ncRNA
Disease	Gastric cancer	Disease Info

m6A Target: Pvt1 oncogene (PVT1)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT05418		Crosstalk Info
Epigenetic Regulator	Pvt1 oncogene (PVT1)
Crosstalk relationship	m6A → ncRNA
Disease	Osteosarcoma	Disease Info
Crosstalk ID: M6ACROT05818		Crosstalk Info
Epigenetic Regulator	Pvt1 oncogene (PVT1)
Crosstalk relationship	m6A → ncRNA
Disease	Diabetic encephalopathy	Disease Info

m6A Target: X inactive specific transcript (XIST)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05420		Crosstalk Info
Epigenetic Regulator	X inactive specific transcript (XIST)
Crosstalk relationship	m6A → ncRNA
Disease	Colorectal cancer	Disease Info

m6A Target: Testis associated oncogenic lncRNA (THORLNC)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05442		Crosstalk Info
Epigenetic Regulator	Testis associated oncogenic lncRNA (THORLNC)
Crosstalk relationship	m6A → ncRNA

m6A Target: hsa-mir-181b-1

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05467		Crosstalk Info
Epigenetic Regulator	hsa-mir-181b-1
Regulated Target	Transcriptional coactivator YAP1 (YAP1)
Crosstalk relationship	m6A → ncRNA
Disease	Osteosarcoma	Disease Info

m6A Target: FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05483		Crosstalk Info
Epigenetic Regulator	FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR)
Regulated Target	Transcription factor SOX-4 (SOX4)
Crosstalk relationship	m6A → ncRNA
Disease	Endometrial cancer	Disease Info

m6A Target: Deleted in lymphocytic leukemia 2 (DLEU2/LINC00022)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05518		Crosstalk Info
Epigenetic Regulator	Deleted in lymphocytic leukemia 2 (DLEU2/LINC00022)
Regulated Target	Cyclin-dependent kinase inhibitor 1 (CDKN1A)
Crosstalk relationship	m6A → ncRNA
Disease	Esophageal Squamous Cell Carcinoma	Disease Info

m6A Target: Nuclear paraspeckle assembly transcript 1 (NEAT1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05539		Crosstalk Info
Epigenetic Regulator	Nuclear paraspeckle assembly transcript 1 (NEAT1)
Crosstalk relationship	m6A → ncRNA
Disease	Renal cell carcinoma	Disease Info

m6A Target: KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05541		Crosstalk Info
Epigenetic Regulator	KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1)
Regulated Target	Homeobox A9 (HOXA9)
Crosstalk relationship	m6A → ncRNA
Disease	Laryngeal cancer	Disease Info

m6A Target: Circ_ASK1

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05585		Crosstalk Info
Epigenetic Regulator	Circ_ASK1
Regulated Target	Mitogen-activated protein kinase kinase kinase 5 (MAP3K5)
Crosstalk relationship	m6A → ncRNA
Disease	Lung cancer	Disease Info
Drug	Gefitinib	Drug Info

m6A Target: hsa-miR-1915-3p

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05609		Crosstalk Info
Epigenetic Regulator	hsa-miR-1915-3p
Regulated Target	Protein SET (SET)
Crosstalk relationship	m6A → ncRNA
Disease	Non-small cell lung cancer	Disease Info

m6A Target: LINC00902 (TUSC7)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05633		Crosstalk Info
Epigenetic Regulator	LINC00902 (TUSC7)
Crosstalk relationship	m6A → ncRNA
Disease	Lung cancer	Disease Info
Drug	Erlotinib	Drug Info

m6A Target: Circ_RERE

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05642		Crosstalk Info
Epigenetic Regulator	Circ_RERE
Regulated Target	hsa-miR-195-5p
Crosstalk relationship	m6A → ncRNA
Disease	Osteoarthritis	Disease Info
Drug	ICG-001	Drug Info

m6A Target: Circ_IRF2

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05650		Crosstalk Info
Epigenetic Regulator	Circ_IRF2
Regulated Target	hsa-miR-29b-1-5p
Crosstalk relationship	m6A → ncRNA
Disease	Hepatic fibrosis/cirrhosis	Disease Info

m6A Target: Cardiac mesoderm enhancer-associated non-coding RNA (CARMN)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05667		Crosstalk Info
Epigenetic Regulator	Cardiac mesoderm enhancer-associated non-coding RNA (CARMN)
Regulated Target	hsa-miR-21-5p
Crosstalk relationship	m6A → ncRNA
Disease	Cervical cancer	Disease Info

m6A Target: microRNA 126 (MIR126)

Target Gene

In total 7 item(s) under this m6A target
Crosstalk ID: M6ACROT05682		Crosstalk Info
Epigenetic Regulator	MicroRNA 126 (MIR126)
Regulated Target	ADAM metallopeptidase domain 9 (ADAM9)
Crosstalk relationship	m6A → ncRNA
Disease	Acute myeloid leukaemia	Disease Info
Crosstalk ID: M6ACROT05925		Crosstalk Info
Epigenetic Regulator	MicroRNA 126 (MIR126)
Regulated Target	Scaffold protein ILK (ILK)
Crosstalk relationship	m6A → ncRNA
Disease	Acute myeloid leukaemia	Disease Info
Crosstalk ID: M6ACROT05927		Crosstalk Info
Epigenetic Regulator	MicroRNA 126 (MIR126)
Regulated Target	Cyclin-dependent kinase 3 (CDK3)
Crosstalk relationship	m6A → ncRNA
Disease	Acute myeloid leukaemia	Disease Info
Crosstalk ID: M6ACROT05933		Crosstalk Info
Epigenetic Regulator	MicroRNA 126 (MIR126)
Regulated Target	Target of Myb1 membrane trafficking protein (TOM1)
Crosstalk relationship	m6A → ncRNA
Disease	Acute myeloid leukaemia	Disease Info
Crosstalk ID: M6ACROT05935		Crosstalk Info
Epigenetic Regulator	MicroRNA 126 (MIR126)
Regulated Target	High affinity immunoglobulin gamma Fc receptor I (FCGR1A)
Crosstalk relationship	m6A → ncRNA
Disease	Acute myeloid leukaemia	Disease Info
Crosstalk ID: M6ACROT05937		Crosstalk Info
Epigenetic Regulator	MicroRNA 126 (MIR126)
Regulated Target	Ficolin-1 (FCN1)
Crosstalk relationship	m6A → ncRNA
Disease	Acute myeloid leukaemia	Disease Info
Crosstalk ID: M6ACROT05939		Crosstalk Info
Epigenetic Regulator	MicroRNA 126 (MIR126)
Regulated Target	Leucine-rich repeat and calponin homology domain-containing protein 4 (LRCH4)
Crosstalk relationship	m6A → ncRNA
Disease	Acute myeloid leukaemia	Disease Info

m6A Target: Circ_AFF2

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05683		Crosstalk Info
Epigenetic Regulator	Circ_AFF2
Regulated Target	Cullin associated and neddylation dissociated 1 (CAND1)
Crosstalk relationship	m6A → ncRNA
Disease	Colorectal cancer	Disease Info

m6A Target: Circ_FUT8

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05692		Crosstalk Info
Epigenetic Regulator	Circ_FUT8
Regulated Target	Fucosyltransferase 8 (FUT8)
Crosstalk relationship	m6A → ncRNA
Disease	Lung cancer	Disease Info

m6A Target: Circ_RNF13

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05707		Crosstalk Info
Epigenetic Regulator	Circ_RNF13
Regulated Target	C-X-C motif chemokine ligand 1 (CXCL1)
Crosstalk relationship	m6A → ncRNA
Disease	Cervical cancer	Disease Info

m6A Target: Circ_GPATCH2L

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05710		Crosstalk Info
Epigenetic Regulator	Circ_GPATCH2L
Regulated Target	Tripartite motif containing 28 (TRIM28)
Crosstalk relationship	m6A → ncRNA
Disease	Spinal pain	Disease Info

m6A Target: microRNA 145 (MIR145)

Target Gene

In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05819		Crosstalk Info
Epigenetic Regulator	MicroRNA 145 (MIR145)
Crosstalk relationship	m6A → ncRNA
Disease	Epilepsy due to structural or metabolic conditions or diseases	Disease Info

m6A Target: Long intergenic non-protein coding RNA 657 (NORAD)

Target Gene

In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT05970		Crosstalk Info
Epigenetic Regulator	Long intergenic non-protein coding RNA 657 (NORAD)
Regulated Target	Pumilio homolog 1 (PUM1)
Crosstalk relationship	m6A → ncRNA
Disease	Intervertebral disc degeneration	Disease Info
Crosstalk ID: M6ACROT05972		Crosstalk Info
Epigenetic Regulator	Long intergenic non-protein coding RNA 657 (NORAD)
Regulated Target	Pumilio homolog 2 (PUM2)
Crosstalk relationship	m6A → ncRNA
Disease	Intervertebral disc degeneration	Disease Info

Xenobiotics Compound(s) Regulating the m6A Methylation Regulator

Compound Name	Rapamycin	Approved
Synonyms	Rapamune; Rapamycin (Sirolimus); AY-22989; Rapammune; sirolimusum; WY-090217; RAPA; Antibiotic AY 22989; AY 22989; UNII-W36ZG6FT64; CCRIS 9024; CHEBI:9168; SILA 9268A; W36ZG6FT64; HSDB 7284; C51H79NO13; NSC 226080; DE-109; NCGC00021305-05; DSSTox_CID_3582; DSSTox_RID_77091; DSSTox_GSID_23582; Cypher; Supralimus; Wy 090217; Perceiva; RAP; RPM; Rapamycin from Streptomyces hygroscopicus; SIIA 9268A; LCP-Siro; MS-R001; Rapamune (TN); Rapamycin (TN); Sirolimus (RAPAMUNE); Rapamycin C-7, analog 4; Sirolimus (USAN/INN); Sirolimus [USAN:BAN:INN]; Sirolimus, Rapamune,Rapamycin; Heptadecahydro-9,27-dihydroxy-3-[(1R)-2-[(1S,3R,4R)-4-hydroxy; 23,27-Epoxy-3H-pyrido(2,1-c)(1,4)oxaazacyclohentriacontine; 23,27-Epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine; 23,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29; 3H-pyrido(2,1-c)(1,4)oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone; Sirolimus (MTOR inhibitor) Click to Show/Hide
External link	CID: 5284616 TTD: D03LJR DrugBank: DB00877
Description	Rapamycin inhibited FTO activity, and directly targetedeIF4G1 transcripts and mediated their expression in an m6A-dependent manner inoral squamous cell carcinoma. After FTO silencing, YTHDF2 captured eIF4G1 transcripts containing m6A, resulting in mRNA degradation and decreased expression of eIF4G1 protein, thereby promoting autophagy and reducing tumor occurrence.	[72]
Compound Name	Linsitinib	Phase 3
Synonyms	Linsitinib; 867160-71-2; OSI-906; Linsitinib(OSI-906); OSI906; OSI 906; OSI-906AA; OSI-906 (Linsitinib); UNII-15A52GPT8T; Kinome_3532; ASP-7487; 3-[8-amino-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutan-1-ol; 15A52GPT8T; CHEMBL1091644; MMV676605; cis-3-[8-Amino-1-(2-phenyl-7-quinolinyl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutanol; C26H23N5O; cis-3-(8-amino-1-(2-phenyl-7-quinolinyl)imidazo(1,5-a)pyrazin-3-yl)-1-methylcyclobutanol; Linsitinib [USAN:INN]; OSI906/Linsitinib/; Linsitinib; OSI-906 Click to Show/Hide
External link	CID: 11640390 TTD: D01GFX DrugBank: DB06075
Description	The m6A reader YTHDF2 stabilizedMYC mRNA specifically in cancer stem cells. Given the challenge of targeting MYC, YTHDF2 presents a therapeutic target to perturb MYC signaling in glioblastoma. The IGF1/IGF1R inhibitor linsitinib preferentially targeted YTHDF2-expressing cells, inhibiting GSC viability without affecting NSCs and impairing in vivoglioblastoma growth. YTHDF2 links RNA epitranscriptomic modifications and GSC growth, laying the foundation for the YTHDF2-MYC-IGFBP3 axis as a specific and novel therapeutic target in glioblastoma.	[11]
Compound Name	PT2385	Phase 2
Synonyms	ONBSHRSJOPSEGS-INIZCTEOSA-N; PT-2385; UNII-6O16716DXP; 1672665-49-4; 6O16716DXP; SCHEMBL16555810; ZINC230453533; AKOS030526641; HY-12867; PT2385,1672665-49-4, PT 2385,PT-2385; Benzonitrile, 3-(((1S)-2,2-difluoro-2,3-dihydro-1-hydroxy-7-(methylsulfonyl)-1H-inden-4-yl)oxy)-5-fluoro-; 3-{[(1s)-2,2-Difluoro-1-Hydroxy-7-(Methylsulfonyl)-2,3-Dihydro-1h-Inden-4-Yl]oxy}-5-Fluorobenzonitrile; 3-(((1S)-2,2-Difluoro-1-hydroxy-7-methanesulfonyl-2,3-dihydro-1hinden-4-yl)oxy)-5-fluorobenzonitrile; 79A Click to Show/Hide
External link	CID: 91754484 TTD: D0C9PZ
Description	YTHDF2 processed the decay of m6A-containinginterleukin 11 (IL11) and serpin family E member 2 (SERPINE2) mRNAs. YTHDF2 transcription succumbed to hypoxia-inducible factor-2-alpha (HIF-2-alpha). Administration of a HIF-2-alpha antagonist (PT2385) restored YTHDF2-programed epigenetic machinery and repressedliver cancer.	[27]
Compound Name	TL13-68	Investigative
Synonyms	TL13-68; CHEMBL4129274; BDBM50269622; HY-136849; CS-0134015 Click to Show/Hide
External link	CID: 145963683
Activity	IC50=33 nM	[201]

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m6A Regulator Information

Cite M6AREG

Correspondence

Prof. Feng ZHU

Prof. Shuiping Liu

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