m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00451)
Target Name Transcriptional coactivator YAP1 (YAP1)
Synonyms
Yes-associated protein 1; Protein yorkie homolog; Yes-associated protein YAP65 homolog; YAP65
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Gene Name YAP1
Chromosomal Location 11q22.1
Family YAP1 family
Function
Transcriptional regulator which can act both as a coactivator and a corepressor and is the critical downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Plays a key role in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation. Acts via ARHGAP18, a Rho GTPase activating protein that suppresses F-actin polymerization. Plays a key role in controlling cell proliferation in response to cell contact. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration . The presence of TEAD transcription factors are required for it to stimulate gene expression, cell growth, anchorage-independent growth, and epithelial mesenchymal transition (EMT) induction. Suppresses ciliogenesis via acting as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1. In conjunction with WWTR1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (By similarity); [Isoform 2]: Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3).
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Gene ID 10413
Uniprot ID
YAP1_HUMAN
HGNC ID
HGNC:16262
Ensembl Gene ID
ENSG00000137693
KEGG ID
hsa:10413
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
YAP1 can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
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Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line LNCaP cell line Homo sapiens
Treatment: shMETTL3 LNCaP cells
Control: shControl LNCaP cells
 GSE147884
Regulation
logFC: 6.80E-01
p-value: 6.99E-58
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between YAP1 and the regulator
Cell Line MDA-MB-231 Homo sapiens
Regulation logFC: 1.22E+00 GSE60213
In total 4 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary The expression of m6A and METTL3 was upregulated in human gastric cancer tissues and gastric cancer cell lines. m6A methyltransferase METTL3 promoted the proliferation and migration of gastric cancer cells through the m6A modification of Transcriptional coactivator YAP1 (YAP1).
Target Regulation Up regulation
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Cell Process Cell proliferation
Cell metastasis
In-vitro Model MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
GES-1 Normal Homo sapiens CVCL_EQ22
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary METTL3-induced circ1662 promoted colorectal cancer cell invasion and migration by accelerating Transcriptional coactivator YAP1 (YAP1) nuclear transport. Circ1662 enhanced CRC invasion and migration depending on YAP1 and SMAD3. This result implies that circ1662 is a new prognostic and therapeutic marker for CRC metastasis.
Target Regulation Up regulation
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Cell invasion
Cell migration
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
In-vivo Model BALB/c nude mice (4 weeks old) were acquired from Vital River Laboratory (Beijing, China). HCT116 cells with stable circ1662 expression (2 × 106 in 100 L of PBS) were injected via the tail vein. After 45 days, the mice were sacrificed. The lung metastatic carcinoma specimens were processed into paraffin-embedded sections for subsequent H&E staining and IHC.
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary m6A methylation plays a key role in VM formation in HCC. METTL3 and Transcriptional coactivator YAP1 (YAP1) could be potential therapeutic targets via impairing VM formation in anti-metastatic strategies.
Target Regulation Up regulation
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Cell migration and invasion
In-vitro Model Homo sapiens (SK-HEP-1-Luc (luciferase labeled) cells were obtained from OBIO (Shanghai, China).)
MHCC97-H Adult hepatocellular carcinoma Homo sapiens CVCL_4972
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
In-vivo Model 1 × 107 SK-HEP-1-Luc-shControl or SK-HEP-1-Luc-shMETTL3 stable cells were suspended in 300 uL of PBS and injected orthotopically into the left liver lobe of nude mice.
Experiment 4 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-Transcriptional coactivator YAP1 (YAP1) axis to induce Non-small cell lung cancer drug resistance and metastasis.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Metabolic
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
YTH domain-containing family protein 1 (YTHDF1) [READER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF1
Cell Line AGS cell line Homo sapiens
Treatment: shYTHDF1 AGS
Control: shNC AGS
 GSE166972
Regulation
logFC: 3.89E+00
p-value: 1.09E-02
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between YAP1 and the regulator
Cell Line Hela Homo sapiens
Regulation logFC: 1.35E+00 GSE63591
In total 3 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [5]
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.
Target Regulation Up regulation
Responsed Disease Osteosarcoma ICD-11: 2B51
 Disease Info 
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.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-Transcriptional coactivator YAP1 (YAP1) axis to induce Non-small cell lung cancer drug resistance and metastasis.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Metabolic
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [6]
Response Summary YTHDF1 knockdown alleviated the progression of renal fibrosis both in cultured cells induced by transforming growth factor-beta administration and in the UUO mouse model. Transcriptional coactivator YAP1 (YAP1) was accordingly down-regulated when YTHDF1 was inhibited.
Target Regulation Up regulation
Responsed Disease Kidney disorders ICD-11: GB90
 Disease Info 
YTH domain-containing family protein 2 (YTHDF2) [READER]
 Regulator Info 
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 YAP1 and the regulator
Cell Line Hela Homo sapiens
Regulation logFC: 1.34E+00 GSE49339
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [5]
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.
Responsed Disease Osteosarcoma ICD-11: 2B51
 Disease Info 
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.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [7]
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.
Target Regulation Down regulation
Responsed Disease Pancreatic cancer ICD-11: 2C10
 Disease Info 
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
Fat mass and obesity-associated protein (FTO) [ERASER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by FTO
Cell Line Cerebral cortex Mus musculus
Treatment: METTL3 (f/f, Emx1-cre) cerebral cortex
Control: Wild type cerebral cortex
 GSE154992
Regulation
logFC: 6.87E-01
p-value: 5.76E-08
More Results Click to View More RNA-seq Results
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [8]
Response Summary Stable knockdown of FTO inhibited OSCC cell viability, colony formation, and tumor growth. Further, FTO depletion increased Transcriptional coactivator YAP1 (YAP1) m6A modification at mRNA 3'-untranslated region, accelerating the degradation of YAP1 mRNA, a well-documented oncogene promoting OSCC progression.
Target Regulation Up regulation
Responsed Disease Oral squamous cell carcinoma ICD-11: 2B6E.0
 Disease Info 
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [9]
Response Summary FTO down-expressed in myocardial IRI mice and hypoxia/reoxygenation (H/R)-induced cardiomyocytes. Moreover, FTO uninstalled the methylation of Transcriptional coactivator YAP1 (YAP1) mRNA, and enforced the stability of Yap1 mRNA.The study reveals the role of FTO in H/R-induced myocardial cell injury via m6A-dependent manner, which provided a new approach to improve myocardial IRI.
Target Regulation Up regulation
Responsed Disease Ischemic heart disease ICD-11: BA40-BA6Z
 Disease Info 
Cell Process Cell apoptosis
In-vitro Model Neonatal rat ventricular cardiomyocytes (Primary myocyte cells)
In-vivo Model After anesthesia (50 mg/kg pentobarbital sodium, intraperitoneal injection), the left thorax was cut to expose the heart, and the left anterior descending (LAD) coronary artery was ligated by 7/0 sterile suture. Myocardial ischemia was induced by 30 min of LAD coronary artery ligation and following 2 h of reperfusion. Sham group mice underwent the same surgical procedure without LAD coronary artery ligation.
Methyltransferase-like 14 (METTL14) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL14
Cell Line MDA-MB-231 Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells
Control: MDA-MB-231 cells
 GSE81164
Regulation
logFC: 1.32E+00
p-value: 8.59E-29
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [10]
Response Summary METTL14 promotes renal ischemic reperfusion injury via suppressing Transcriptional coactivator YAP1 (YAP1).
Target Regulation Down regulation
Responsed Disease Injury of kidney ICD-11: NB92.0
 Disease Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Cell proliferation and metastasis
In-vitro Model HK2 Normal Acipenser baerii CVCL_YE28
RNA demethylase ALKBH5 (ALKBH5) [ERASER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5
Cell Line 143B cell line Homo sapiens
Treatment: siALKBH5 transfected 143B cells
Control: siControl 143B cells
 GSE154528
Regulation
logFC: -6.56E-01
p-value: 3.77E-04
More Results Click to View More RNA-seq Results
In total 3 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [5]
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.
Target Regulation Down regulation
Responsed Disease Osteosarcoma ICD-11: 2B51
 Disease Info 
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.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [11]
Response Summary m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated Transcriptional coactivator YAP1 (YAP1) expression and inhibiting miR-107/LATS2-mediated YAP activity in non-small cell lung cancer.
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Cell Process Cell proliferation
Cell invasion
Cell migration
Cell EMT
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
BEAS-2B Normal Homo sapiens CVCL_0168
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model For the experiments, mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into indicated groups (five mice per group). To assess the in vivo effects of cycloleucine, the xenografted tumors had reached approximately 5 mm in diameter from mice and then these xenografted mice were feed with Vehicle or cycloleucine (25 mg/kg twice weekly) and tumor volume were measured every 3 day. Tumor volume was estimated as 0.5 × a2 × b (where a and b represent a tumors short and long diameter, respectively). Mice were euthanized after 7 weeks and the tumors were measured a final time.
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [12]
Response Summary ALKBH5-mediated m6A demethylation improved the mRNA stability of YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1), thereby increasing its expression, which consequently promoted the translation of Transcriptional coactivator YAP1 (YAP1).This finding suggests a novel potential therapeutic strategy for myocardial infarction cardiac regeneration.
Target Regulation Up regulation
Responsed Disease Acute myocardial infarction ICD-11: BA41
 Disease Info 
In-vivo Model Cas9 and sgRNA were microinjected into the fertilized eggs of C57BL/6J mice, which were then transplanted to obtain positive F0 mice. The statuses of F0 mice were confirmed by PCR and sequencing. Next, positive F0 mice were mated with C57BL/6J mice to yield stable F1 generation mice. F1 and F2 transgenic mice were used in this study.
YTH domain-containing family protein 3 (YTHDF3) [READER]
 Regulator Info 
Representative RIP-seq result supporting the interaction between YAP1 and the regulator
Cell Line Hela Homo sapiens
Regulation logFC: 1.33E+00 GSE86214
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-Transcriptional coactivator YAP1 (YAP1) axis to induce Non-small cell lung cancer drug resistance and metastasis.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Metabolic
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Eukaryotic initiation factor 3 (EIF3A) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [11]
Response Summary YTHDF1 promoted Transcriptional coactivator YAP1 (YAP1) mRNA translation by interacting with eIF3a in NSCLC.
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
In-vitro Model BEAS-2B Normal Homo sapiens CVCL_0168
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model 3 to 5-week old female BALB/c athymic (NU/NU) nude mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into indicated groups (five mice per group). To assess the in vivo effects of cycloleucine, the xenografted tumors had reached approximately 5 mm in diameter from mice and then these xenografted mice were feed with Vehicle or cycloleucine (25 mg/kg twice weekly) and tumor volume were measured every 3 day.
Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [13]
Response Summary IGF2BP2 activates the expression of ErbB2 by recognizing the m6A of Transcriptional coactivator YAP1 (YAP1), thus affecting the cell cycle of colorectal cancer, inhibiting cell apoptosis, and promoting proliferation.
Target Regulation Up regulation
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Responsed Drug Temozolomide Approved
 Drug Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Cell apoptosis
In-vitro Model HCT 8 Colon adenocarcinoma Homo sapiens CVCL_2478
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
In-vivo Model IGF2BP2 activates the expression of ErbB2 by recognizing the m6A of YAP, thus affecting the cell cycle of CRC, inhibiting cell apoptosis, and promoting proliferation.
YTH domain-containing protein 2 (YTHDC2) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [14]
Response Summary High YTHDC2 was strongly positively correlated with high Transcriptional coactivator YAP1 (YAP1) in clinical GC tissues, YTHDC2 is a novel oncogene in GC, which provides the theoretical basis for the strategy of targeting YTHDC2 for GC patients.
Target Regulation Up regulation
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
In-vitro Model HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model They were subcutaneously and caudal vein injected with YTHDC2 knockout AGS cells, respectively. After 7 weeks, the mice were sacrificed and tumor size and lung metastasis nodules were recorded.
Osteosarcoma [ICD-11: 2B51]
 Disease Info 
In total 3 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [5]
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.
Responsed Disease Osteosarcoma [ICD-11: 2B51]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
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.
Experiment 2 Reporting the m6A-centered Disease Response [5]
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.
Responsed Disease Osteosarcoma [ICD-11: 2B51]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Cell Process Cell growth
Cell migration
Cell invasion
Cell apoptosis
In-vitro Model U2OS Osteosarcoma Homo sapiens CVCL_0042
In-vivo Model Three-week-old BABL/c female nude mice were randomized into three groups. 5 × 106 143B cells were subcutaneously injected in mice, and the tumor volume was assessed every 2 weeks. Eight weeks after injection, the animals were killed. The xenograft tumors were harvested and the tumor volumes were calculated by the standard formula: length × width2/2.
Experiment 3 Reporting the m6A-centered Disease Response [5]
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.
Responsed Disease Osteosarcoma [ICD-11: 2B51]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
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.
Head and neck squamous carcinoma [ICD-11: 2B6E]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [8]
Response Summary Stable knockdown of FTO inhibited OSCC cell viability, colony formation, and tumor growth. Further, FTO depletion increased Transcriptional coactivator YAP1 (YAP1) m6A modification at mRNA 3'-untranslated region, accelerating the degradation of YAP1 mRNA, a well-documented oncogene promoting OSCC progression.
Responsed Disease Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Up regulation
Gastric cancer [ICD-11: 2B72]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary The expression of m6A and METTL3 was upregulated in human gastric cancer tissues and gastric cancer cell lines. m6A methyltransferase METTL3 promoted the proliferation and migration of gastric cancer cells through the m6A modification of Transcriptional coactivator YAP1 (YAP1).
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Cell Process Cell proliferation
Cell metastasis
In-vitro Model MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
GES-1 Normal Homo sapiens CVCL_EQ22
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
Experiment 2 Reporting the m6A-centered Disease Response [14]
Response Summary High YTHDC2 was strongly positively correlated with high Transcriptional coactivator YAP1 (YAP1) in clinical GC tissues, YTHDC2 is a novel oncogene in GC, which provides the theoretical basis for the strategy of targeting YTHDC2 for GC patients.
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulator YTH domain-containing protein 2 (YTHDC2) READER
 Regulator Info 
Target Regulation Up regulation
In-vitro Model HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model They were subcutaneously and caudal vein injected with YTHDC2 knockout AGS cells, respectively. After 7 weeks, the mice were sacrificed and tumor size and lung metastasis nodules were recorded.
Colorectal cancer [ICD-11: 2B91]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [13]
Response Summary IGF2BP2 activates the expression of ErbB2 by recognizing the m6A of Transcriptional coactivator YAP1 (YAP1), thus affecting the cell cycle of colorectal cancer, inhibiting cell apoptosis, and promoting proliferation.
Responsed Disease Colorectal cancer [ICD-11: 2B91]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) READER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug Temozolomide Approved
 Drug Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Cell apoptosis
In-vitro Model HCT 8 Colon adenocarcinoma Homo sapiens CVCL_2478
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
In-vivo Model IGF2BP2 activates the expression of ErbB2 by recognizing the m6A of YAP, thus affecting the cell cycle of CRC, inhibiting cell apoptosis, and promoting proliferation.
Experiment 2 Reporting the m6A-centered Disease Response [2]
Response Summary METTL3-induced circ1662 promoted colorectal cancer cell invasion and migration by accelerating Transcriptional coactivator YAP1 (YAP1) nuclear transport. Circ1662 enhanced CRC invasion and migration depending on YAP1 and SMAD3. This result implies that circ1662 is a new prognostic and therapeutic marker for CRC metastasis.
Responsed Disease Colorectal cancer [ICD-11: 2B91]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Hippo signaling pathway hsa04390
Cell Process Cell invasion
Cell migration
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
In-vivo Model BALB/c nude mice (4 weeks old) were acquired from Vital River Laboratory (Beijing, China). HCT116 cells with stable circ1662 expression (2 × 106 in 100 L of PBS) were injected via the tail vein. After 45 days, the mice were sacrificed. The lung metastatic carcinoma specimens were processed into paraffin-embedded sections for subsequent H&E staining and IHC.
Pancreatic cancer [ICD-11: 2C10]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [7]
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.
Responsed Disease Pancreatic cancer [ICD-11: 2C10]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
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
Liver cancer [ICD-11: 2C12]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary m6A methylation plays a key role in VM formation in HCC. METTL3 and Transcriptional coactivator YAP1 (YAP1) could be potential therapeutic targets via impairing VM formation in anti-metastatic strategies.
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Hippo signaling pathway hsa04390
Cell Process Cell migration and invasion
In-vitro Model Homo sapiens (SK-HEP-1-Luc (luciferase labeled) cells were obtained from OBIO (Shanghai, China).)
MHCC97-H Adult hepatocellular carcinoma Homo sapiens CVCL_4972
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
In-vivo Model 1 × 107 SK-HEP-1-Luc-shControl or SK-HEP-1-Luc-shMETTL3 stable cells were suspended in 300 uL of PBS and injected orthotopically into the left liver lobe of nude mice.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 5 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [11]
Response Summary YTHDF1 promoted Transcriptional coactivator YAP1 (YAP1) mRNA translation by interacting with eIF3a in NSCLC.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator Eukaryotic initiation factor 3 (EIF3A) READER
 Regulator Info 
Target Regulation Up regulation
In-vitro Model BEAS-2B Normal Homo sapiens CVCL_0168
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model 3 to 5-week old female BALB/c athymic (NU/NU) nude mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into indicated groups (five mice per group). To assess the in vivo effects of cycloleucine, the xenografted tumors had reached approximately 5 mm in diameter from mice and then these xenografted mice were feed with Vehicle or cycloleucine (25 mg/kg twice weekly) and tumor volume were measured every 3 day.
Experiment 2 Reporting the m6A-centered Disease Response [4]
Response Summary METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-Transcriptional coactivator YAP1 (YAP1) axis to induce Non-small cell lung cancer drug resistance and metastasis.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Metabolic
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Experiment 3 Reporting the m6A-centered Disease Response [11]
Response Summary m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated Transcriptional coactivator YAP1 (YAP1) expression and inhibiting miR-107/LATS2-mediated YAP activity in non-small cell lung cancer.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Cell Process Cell proliferation
Cell invasion
Cell migration
Cell EMT
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
BEAS-2B Normal Homo sapiens CVCL_0168
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model For the experiments, mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into indicated groups (five mice per group). To assess the in vivo effects of cycloleucine, the xenografted tumors had reached approximately 5 mm in diameter from mice and then these xenografted mice were feed with Vehicle or cycloleucine (25 mg/kg twice weekly) and tumor volume were measured every 3 day. Tumor volume was estimated as 0.5 × a2 × b (where a and b represent a tumors short and long diameter, respectively). Mice were euthanized after 7 weeks and the tumors were measured a final time.
Experiment 4 Reporting the m6A-centered Disease Response [4]
Response Summary METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-Transcriptional coactivator YAP1 (YAP1) axis to induce Non-small cell lung cancer drug resistance and metastasis.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Metabolic
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Experiment 5 Reporting the m6A-centered Disease Response [4]
Response Summary METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-Transcriptional coactivator YAP1 (YAP1) axis to induce Non-small cell lung cancer drug resistance and metastasis.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator YTH domain-containing family protein 3 (YTHDF3) READER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Metabolic
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Ischemic heart disease [ICD-11: BA40-BA6Z]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [9]
Response Summary FTO down-expressed in myocardial IRI mice and hypoxia/reoxygenation (H/R)-induced cardiomyocytes. Moreover, FTO uninstalled the methylation of Transcriptional coactivator YAP1 (YAP1) mRNA, and enforced the stability of Yap1 mRNA.The study reveals the role of FTO in H/R-induced myocardial cell injury via m6A-dependent manner, which provided a new approach to improve myocardial IRI.
Responsed Disease Ischemic heart disease [ICD-11: BA40-BA6Z]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Up regulation
Cell Process Cell apoptosis
In-vitro Model Neonatal rat ventricular cardiomyocytes (Primary myocyte cells)
In-vivo Model After anesthesia (50 mg/kg pentobarbital sodium, intraperitoneal injection), the left thorax was cut to expose the heart, and the left anterior descending (LAD) coronary artery was ligated by 7/0 sterile suture. Myocardial ischemia was induced by 30 min of LAD coronary artery ligation and following 2 h of reperfusion. Sham group mice underwent the same surgical procedure without LAD coronary artery ligation.
Acute myocardial infarction [ICD-11: BA41]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [12]
Response Summary ALKBH5-mediated m6A demethylation improved the mRNA stability of YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1), thereby increasing its expression, which consequently promoted the translation of Transcriptional coactivator YAP1 (YAP1).This finding suggests a novel potential therapeutic strategy for myocardial infarction cardiac regeneration.
Responsed Disease Acute myocardial infarction [ICD-11: BA41]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Target Regulation Up regulation
In-vivo Model Cas9 and sgRNA were microinjected into the fertilized eggs of C57BL/6J mice, which were then transplanted to obtain positive F0 mice. The statuses of F0 mice were confirmed by PCR and sequencing. Next, positive F0 mice were mated with C57BL/6J mice to yield stable F1 generation mice. F1 and F2 transgenic mice were used in this study.
Kidney disorders [ICD-11: GB90]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [6]
Response Summary YTHDF1 knockdown alleviated the progression of renal fibrosis both in cultured cells induced by transforming growth factor-beta administration and in the UUO mouse model. Transcriptional coactivator YAP1 (YAP1) was accordingly down-regulated when YTHDF1 was inhibited.
Responsed Disease Kidney disorders [ICD-11: GB90]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Urinary/pelvic organs injury [ICD-11: NB92]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [10]
Response Summary METTL14 promotes renal ischemic reperfusion injury via suppressing Transcriptional coactivator YAP1 (YAP1).
Responsed Disease Injury of kidney [ICD-11: NB92.0]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response Hippo signaling pathway hsa04390
Cell Process Cell proliferation and metastasis
In-vitro Model HK2 Normal Acipenser baerii CVCL_YE28
Cisplatin [Approved]
 Drug Info 
In total 3 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [4]
Response Summary METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-Transcriptional coactivator YAP1 (YAP1) axis to induce Non-small cell lung cancer drug resistance and metastasis.
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Metabolic
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Experiment 2 Reporting the m6A-centered Drug Response [4]
Response Summary METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-Transcriptional coactivator YAP1 (YAP1) axis to induce Non-small cell lung cancer drug resistance and metastasis.
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Metabolic
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Experiment 3 Reporting the m6A-centered Drug Response [4]
Response Summary METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo.m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-Transcriptional coactivator YAP1 (YAP1) axis to induce Non-small cell lung cancer drug resistance and metastasis.
Target Regulator YTH domain-containing family protein 3 (YTHDF3) READER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Metabolic
In-vitro Model A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
Calu-6 Lung adenocarcinoma Homo sapiens CVCL_0236
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H520 Lung squamous cell carcinoma Homo sapiens CVCL_1566
In-vivo Model Mice were injected with 5 × 106 lung cancer cells with stably expression of relevant plasmids and randomly divided into two groups (five mice per group) after the diameter of the xenografted tumors had reached approximately 5 mm in diameter. Xenografted mice were then administrated with PBS or DDP (3 mg/kg per day) for three times a week, and tumor volume were measured every second day.
Temozolomide [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [13]
Response Summary IGF2BP2 activates the expression of ErbB2 by recognizing the m6A of Transcriptional coactivator YAP1 (YAP1), thus affecting the cell cycle of colorectal cancer, inhibiting cell apoptosis, and promoting proliferation.
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) READER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Pathway Response Hippo signaling pathway hsa04390
Cell Process Cell apoptosis
In-vitro Model HCT 8 Colon adenocarcinoma Homo sapiens CVCL_2478
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
In-vivo Model IGF2BP2 activates the expression of ErbB2 by recognizing the m6A of YAP, thus affecting the cell cycle of CRC, inhibiting cell apoptosis, and promoting proliferation.
References
Ref 1 m6A Methyltransferase 3 Promotes the Proliferation and Migration of Gastric Cancer Cells through the m6A Modification of YAP1. J Oncol. 2021 Aug 4;2021:8875424. doi: 10.1155/2021/8875424. eCollection 2021.
Ref 2 N6-methyladenosine-induced circ1662 promotes metastasis of colorectal cancer by accelerating YAP1 nuclear localization. Theranostics. 2021 Feb 25;11(9):4298-4315. doi: 10.7150/thno.51342. eCollection 2021.
Ref 3 RNA m6A methylation promotes the formation of vasculogenic mimicry in hepatocellular carcinoma via Hippo pathway. Angiogenesis. 2021 Feb;24(1):83-96. doi: 10.1007/s10456-020-09744-8. Epub 2020 Sep 13.
Ref 4 m(6)A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-YAP axis to induce NSCLC drug resistance and metastasis. J Hematol Oncol. 2019 Dec 9;12(1):135. doi: 10.1186/s13045-019-0830-6.
Ref 5 ALKBH5 suppresses tumor progression via an m(6)A-dependent epigenetic silencing of pre-miR-181b-1/YAP signaling axis in osteosarcoma. Cell Death Dis. 2021 Jan 11;12(1):60. doi: 10.1038/s41419-020-03315-x.
Ref 6 Involvement of YTHDF1 in renal fibrosis progression via up-regulating YAP. FASEB J. 2022 Feb;36(2):e22144. doi: 10.1096/fj.202100172RR.
Ref 7 YTH domain family 2 orchestrates epithelial-mesenchymal transition/proliferation dichotomy in pancreatic cancer cells. Cell Cycle. 2017;16(23):2259-2271. doi: 10.1080/15384101.2017.1380125. Epub 2017 Nov 14.
Ref 8 FTO demethylates YAP mRNA promoting oral squamous cell carcinoma tumorigenesis. Neoplasma. 2022 Jan;69(1):71-79. doi: 10.4149/neo_2021_210716N967. Epub 2021 Nov 16.
Ref 9 m(6)A demethylase FTO regulates the apoptosis and inflammation of cardiomyocytes via YAP1 in ischemia-reperfusion injury. Bioengineered. 2022 Mar;13(3):5443-5452. doi: 10.1080/21655979.2022.2030572.
Ref 10 The N6-methyladenosine mRNA methylase METTL14 promotes renal ischemic reperfusion injury via suppressing YAP1. J Cell Biochem. 2020 Jan;121(1):524-533. doi: 10.1002/jcb.29258. Epub 2019 Jul 18.
Ref 11 m(6)A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2-mediated YAP activity in NSCLC. Mol Cancer. 2020 Feb 27;19(1):40. doi: 10.1186/s12943-020-01161-1.
Ref 12 ALKBH5 regulates cardiomyocyte proliferation and heart regeneration by demethylating the mRNA of YTHDF1. Theranostics. 2021 Jan 1;11(6):3000-3016. doi: 10.7150/thno.47354. eCollection 2021.
Ref 13 IGF2BP2 promotes the progression of colorectal cancer through a YAP-dependent mechanism. Cancer Sci. 2021 Oct;112(10):4087-4099. doi: 10.1111/cas.15083. Epub 2021 Aug 3.
Ref 14 The N6-methyladenosine reader protein YTHDC2 promotes gastric cancer progression via enhancing YAP mRNA translation. Transl Oncol. 2022 Feb;16:101308. doi: 10.1016/j.tranon.2021.101308. Epub 2021 Dec 12.