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
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Gene Name YTHDF2
Sequence
MSASSLLEQRPKGQGNKVQNGSVHQKDGLNDDDFEPYLSPQARPNNAYTAMSDSYLPSYY
SPSIGFSYSLGEAAWSTGGDTAMPYLTSYGQLSNGEPHFLPDAMFGQPGALGSTPFLGQH
GFNFFPSGIDFSAWGNNSSQGQSTQSSGYSSNYAYAPSSLGGAMIDGQSAFANETLNKAP
GMNTIDQGMAALKLGSTEVASNVPKVVGSAVGSGSITSNIVASNSLPPATIAPPKPASWA
DIASKPAKQQPKLKTKNGIAGSSLPPPPIKHNMDIGTWDNKGPVAKAPSQALVQNIGQPT
QGSPQPVGQQANNSPPVAQASVGQQTQPLPPPPPQPAQLSVQQQAAQPTRWVAPRNRGSG
FGHNGVDGNGVGQSQAGSGSTPSEPHPVLEKLRSINNYNPKDFDWNLKHGRVFIIKSYSE
DDIHRSIKYNIWCSTEHGNKRLDAAYRSMNGKGPVYLLFSVNGSGHFCGVAEMKSAVDYN
TCAGVWSQDKWKGRFDVRWIFVKDVPNSQLRHIRLENNENKPVTNSRDTQEVPLEKAKQV
LKIIASYKHTTSIFDDFSHYEKRQEEEESVKKERQGRGK
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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.
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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 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
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
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.
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 Glioblastoma [ICD-11: 2A00.00]
Responsed Drug Linsitinib Phase 3
 Drug Info 
Target Regulation Up regulation
In-vitro Model
 NSC11 (Pluripotent derived neural progenitor cell)
NHA (Normal human astrocytes)
HNP1 (A human neural progenitor cell)
ENSA (A human embryonic stem derived neural progenitor cell)
In-vivo Model Implanting 5000 human derived GSCs into the right cerebral cortex of NSG mice at a depth of 3.5 mm under a University of California, San Diego Institutional Animal Care and Use Committee (IACUC) approved protocol. Brains were harvested and fixed in 4% formaldehyde, cryopreserved in 30% sucrose, and then cryosectioned. Hematoxylin and eosin (H&E) staining was performed on sections for histological analysis. In parallel survival experiments, mice were observed until the development of neurological signs. 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. Mice recovered for 7 days were randomly assigned into drug vs. treatment group by a blinded investigator. Mice were then treated daily with either vehicle (25 mM Tartaric acid) or 50 mg/kg linsitinib by oral gavage.
Response Summary The IGF1/IGF1R inhibitor, linsitinib for further investigation based upon the role of the IGF pathway member, IGFBP3, as a downstream effector of YTHDF2-Myc proto-oncogene protein (MYC) axis in GSCs. Inhibiting glioblastoma stem cells viability without affecting NSCs and impairing in vivo glioblastoma growth.
Experiment 2 Reporting the m6A-centered Disease Response of This Target Gene [11]
Responsed Disease Glioma [ICD-11: 2A00.0]
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.
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 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;Ythdf2fl/fl and Ythdf2fl/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.
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 Bmal1f/f-AlbCre-knockout mice were purchased from Jackson Laboratory. C57BI/6J or Bmal1f/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
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.
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
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.
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.
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 Bmal1f/f-AlbCre-knockout mice were purchased from Jackson Laboratory. C57BI/6J or Bmal1f/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
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
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 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.
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.
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
Oral cavity/oesophagus/stomach in situ carcinoma [ICD-11: 2E60]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [34]
Responsed Disease Esophageal squamous cell carcinoma [ICD-11: 2B70.1]
Target Regulation Down regulation
Pathway Response Cell cycle hsa04110
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.
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 (Ftoflox/flox) and adipose-selective fto knockout (Fabp4-Cre Ftoflox/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.
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
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
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 [47]
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).
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 [48]
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.
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 [49]
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 [49]
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 [49]
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 [49]
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 [49]
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 [49]
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 [50]
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 [51]
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 [52]
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 [51]
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 [52]
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.
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 [53]
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 [54]
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 [55]
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.
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 [56]
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 [57]
Responsed Disease Oral squamous cell carcinoma [ICD-11: 2B6E.0]
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.
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 
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 [58]
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 [59]
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.
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
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.
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
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 
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 [60]
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.
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 [61]
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 [62]
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
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.
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 [63]
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.
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.
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 [49]
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 [49]
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 [49]
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 [49]
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 [49]
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 [49]
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.
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 [64]
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 [65]
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.
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 [59]
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.
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
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 [63]
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 [56]
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 (Ftoflox/flox) and adipose-selective fto knockout (Fabp4-Cre Ftoflox/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.
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 [61]
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 [66]
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.
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 [67]
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 [68]
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
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 [69]
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 [70]
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 [71]
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.
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.
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 [55]
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.
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 [72]
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.
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 [73]
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.
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 [74]
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 [75]
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 [76]
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 [77]
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 [79]
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 [80]
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 [81]
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 [82]
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 [83]
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 Ythdf2fl/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 [84]
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 [85]
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.
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 [86]
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
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 Glioblastoma ICD-11: 2A00.00
 Disease Info 
Target Regulation Up regulation
In-vitro Model NSC11 (Pluripotent derived neural progenitor cell)
NHA (Normal human astrocytes)
HNP1 (A human neural progenitor cell)
ENSA (A human embryonic stem derived neural progenitor cell)
In-vivo Model Implanting 5000 human derived GSCs into the right cerebral cortex of NSG mice at a depth of 3.5 mm under a University of California, San Diego Institutional Animal Care and Use Committee (IACUC) approved protocol. Brains were harvested and fixed in 4% formaldehyde, cryopreserved in 30% sucrose, and then cryosectioned. Hematoxylin and eosin (H&E) staining was performed on sections for histological analysis. In parallel survival experiments, mice were observed until the development of neurological signs. 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. Mice recovered for 7 days were randomly assigned into drug vs. treatment group by a blinded investigator. Mice were then treated daily with either vehicle (25 mM Tartaric acid) or 50 mg/kg linsitinib by oral gavage.
Response Summary The IGF1/IGF1R inhibitor, linsitinib for further investigation based upon the role of the IGF pathway member, IGFBP3, as a downstream effector of YTHDF2-Myc proto-oncogene protein (MYC) axis in GSCs. Inhibiting glioblastoma stem cells viability without affecting NSCs and impairing in vivo glioblastoma growth.
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 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;Ythdf2fl/fl and Ythdf2fl/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 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
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
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 [47]
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).
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 [49]
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 [49]
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 [49]
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 [49]
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 [49]
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 [49]
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 [51]
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 [51]
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.
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 [53]
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.
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.
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 [49]
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 [49]
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 [49]
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 [49]
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 [49]
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 [49]
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.
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 [67]
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 [68]
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
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.
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 [72]
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.
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 [76]
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
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)
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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.
[57]
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
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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
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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
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External link
CID: 145963683
Activity
IC50=33 nM
 [87]
References
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