m6A Regulator Information

General Information of the m6A Regulator (ID: REG00009)

Regulator Name	Wilms tumor 1-associating protein (WTAP)
Synonyms	Female-lethal(2)D homolog; hFL(2)D; WT1-associated protein; Pre-mRNA-splicing regulator WTAP; KIAA0105 Click to Show/Hide
Gene Name	WTAP
Sequence	MTNEEPLPKKVRLSETDFKVMARDELILRWKQYEAYVQALEGKYTDLNSNDVTGLRESEE KLKQQQQESARRENILVMRLATKEQEMQECTTQIQYLKQVQQPSVAQLRSTMVDPAINLF FLKMKGELEQTKDKLEQAQNELSAWKFTPDSQTGKKLMAKCRMLIQENQELGRQLSQGRI AQLEAELALQKKYSEELKSSQDELNDFIIQLDEEVEGMQSTILVLQQQLKETRQQLAQYQ QQQSQASAPSTSRTTASEPVEQSEATSKDCSRLTNGPSNGSSSRQRTSGSGFHREGNTTE DDFPSSPGNGNKSSNSSEERTGRGGSGYVNQLSAGYESVDSPTGSENSLTHQSNDTDSSH DPQEEKAVSGKGNRTVGSRHVQNGLDSSVNVQGSVL Click to Show/Hide
Family	fl(2)d family
Function	Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing . Required for accumulation of METTL3 and METTL14 to nuclear speckle. Acts as a mRNA splicing regulator. Regulates G2/M cell-cycle transition by binding to the 3' UTR of CCNA2, which enhances its stability. Impairs WT1 DNA-binding ability and inhibits expression of WT1 target genes. Click to Show/Hide
Gene ID	9589
Uniprot ID	FL2D_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)

WTAP 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

Alpha-enolase (ENO1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	Human umbilical vein endothelial cells	Homo sapiens
Treatment: siWTAP HUVECs Control: siControl HUVECs		GSE167067
Regulation		logFC: -6.99E-01 p-value: 1.98E-02
More Results	Click to View More RNA-seq Results

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[1]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Target Regulation	Up regulation
Pathway Response	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glycolysis
In-vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	HEK293T	Normal	Homo sapiens	CVCL_0063
In-vivo Model	A total of 1 × 10⁶ luciferase-labeled BC cells transfected with shWTAP or shNC were injected subcutaneously with or without C5aR1 neutrophils (tumor cells:neutrophils, 10:1).
Response Summary	The stabilization of WTAP further promotes RNA m6A methylation of Alpha-enolase (ENO1), impacting the glycolytic activity of BC cells.

AMPK subunit alpha-1 (AMPK/PRKAA1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mice hepatocyte	Mus musculus
Treatment: Wtap Hknockout mice hepatocyte Control: Wtap flox/flox mice hepatocyte		GSE168850
Regulation		logFC: 6.89E-01 p-value: 3.35E-03
More Results	Click to View More RNA-seq Results

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[2]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Pathway Response	AMPK signaling pathway			hsa04152
Pathway Response	Autophagy			hsa04140
Cell Process	Cell autophagy
In-vitro Model	BEL-7402	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
	BEL-7404	Endocervical adenocarcinoma	Homo sapiens	CVCL_6568
	HEK293T	Normal	Homo sapiens	CVCL_0063
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
Response Summary	WTAP/LKB1/AMPK subunit alpha-1 (AMPK/PRKAA1) axis in hepatocellular carcinoma cells acted as a key regulator, linking m6A with autophagy. WTAP-mediated m6A modification plays an important role in the regulation of autophagy in hepatocellular carcinoma cells, which provides a promising target for the treatment of hepatocellular carcinoma.

Caveolin-1 (CAV1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mice hepatocyte	Mus musculus
Treatment: Wtap Hknockout mice hepatocyte Control: Wtap flox/flox mice hepatocyte		GSE168850
Regulation		logFC: 6.32E-01 p-value: 2.97E-02
More Results	Click to View More RNA-seq Results

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				[3]
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulation	Down regulation
Pathway Response	NF-kappa B signaling pathway			hsa04064
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	Ishikawa	Endometrial adenocarcinoma	Homo sapiens	CVCL_2529
	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293
Response Summary	WTAP could methylate 3'-UTR of Caveolin-1 (CAV1) and downregulate CAV-1 expression to activate NF-Kappa-B signaling pathway in EC, which promoted EC progression.

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

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mice hepatocyte	Mus musculus
Treatment: Wtap Hknockout mice hepatocyte Control: Wtap flox/flox mice hepatocyte		GSE168850
Regulation		logFC: 7.14E-01 p-value: 2.43E-02
More Results	Click to View More RNA-seq Results

Acute myocardial infarction [ICD-11: BA41]

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	Acute myocardial infarction [ICD-11: BA41]
Target Regulation	Up regulation
Cell Process	Endoplasmic reticulum stress
	Cell apoptosis
In-vitro Model	AC16 [Human hybrid cardiomyocyte]	Normal	Homo sapiens	CVCL_4U18
In-vivo Model	Left anterior descending coronary artery (LAD) was ligated for 20 minutes, followed by 48 h reperfusion. Controls underwent same procedures except LAD ligation. WTAP shRNA vector or its negative control (shNC) was injected into the left ventricular anterior wall 24 h before I/R. A pressure volume catheter was used for cardiac function assay.
Response Summary	Myocardial infarction (MI) is one of the leading causes of death. WTAP promoted myocardial I/R injury through promoting ER stress and cell apoptosis by regulating m6A modification of Cyclic AMP-dependent transcription factor ATF-4 (ATF4) mRNA. H/R effects on ER stress and apoptosis were all blocked by silencing of WTAP, promoted by WTAP overexpression, and ameliorated by administration of ER stress inhibitor, 4-PBA.

Dual specificity protein phosphatase 6 (DUSP6)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: WTAP-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -6.99E-01 p-value: 7.61E-15
More Results	Click to View More RNA-seq Results

Malignant haematopoietic neoplasm [ICD-11: 2B33]

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	Malignant haematopoietic neoplasm [ICD-11: 2B33]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	Normal NK cells (CD3-negative lymphocytes)
	SNK-6	Nasal type extranodal NK/T-cell lymphoma	Homo sapiens	CVCL_A673
	YTS	Lymphoblastic leukemia/lymphoma	Homo sapiens	CVCL_D324
Response Summary	m6A methyltransferase Wilms' tumor 1-associated protein facilitates cell proliferation and cisplatin resistance in NK/T cell lymphoma by regulating dual-specificity phosphatases 6 expression via m6A RNA methylation. WTAP enhanced Dual specificity protein phosphatase 6 (DUSP6) expression by increasing m6A levels of DUSP6 mRNA transcript, leading to oncogenic functions in NKTCL.

Focal adhesion kinase 1 (Fak)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: WTAP-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 5.98E-01 p-value: 1.29E-24
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				[6]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Responsed Drug	Gemcitabine		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	RNA stability
In-vitro Model	T3M-4	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_4056
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	hTERT-HPNE	Normal	Homo sapiens	CVCL_C466
	HPDE6c7	Normal	Homo sapiens	CVCL_0P38
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
In-vivo Model	Twenty-four female BALB/c athymic nude mice, which were 4-6 weeks old and weighed 20.0-25.0 g, were obtained from the Animal Research Center of PUMCH. WTAP-OE, WTAP-NC, shWTAP and shNC-lentivirus infected MIA PaCa-2 cells (5 × 10⁶) were suspended in 50 uL PBS and then injected subcapsularly into the pancreatic tissue by 1-mL syringes.
Response Summary	WTAP could promote migration/invasion and suppress chemo-sensitivity to gemcitabine in PC. Further mechanical investigation revealed that WTAP could bind to and stabilize Focal adhesion kinase 1 (Fak) mRNA which in turn activated the Fak-PI3K-AKT and Fak-Src-GRB2-Erk1/2 signaling pathways.

Forkhead box protein M1 (FOXM1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: WTAP-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -9.85E-01 p-value: 1.39E-67
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				[7]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Up regulation
In-vitro Model	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
In-vivo Model	In vivo animal assay, FOXD2-AS1 overexpression promoted the tumor growth in mice subcutaneous injection
Response Summary	A remarkable m6A-modified site was found on the 3'-UTR of FOXD2-AS1, and m6A methyltransferase WTAP promoted the methylation modification, thus enhancing the stability of FOXD2-AS1 transcripts. m6A-modified FOXD2-AS1 accelerates the osteosarcoma progression through m6A manner, which provides new concepts for osteosarcoma tumorigenesis. FOXD2-AS1 interacted with downstream target FOXM1 mRNA through m6A sites, forming a FOXD2-AS1/m6A/Forkhead box protein M1 (FOXM1) complex to heighten FOXM1 mRNA stability.

Hepatocyte growth factor receptor (c-Met/MET)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: WTAP-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -2.39E+00 p-value: 1.81E-38
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				[8]
Responsed Disease	Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Responsed Drug	Crizotinib		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	EGFR tyrosine kinase inhibitor resistance			hsa01521
In-vitro Model	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	NCI-H661	Lung large cell carcinoma	Homo sapiens	CVCL_1577
	NCI-H596	Lung adenosquamous carcinoma	Homo sapiens	CVCL_1571
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H358	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1559
	NCI-H292	Lung mucoepidermoid carcinoma	Homo sapiens	CVCL_0455
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1395	Lung adenocarcinoma	Homo sapiens	CVCL_1467
	EBC-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_2891
	Calu-3	Lung adenocarcinoma	Homo sapiens	CVCL_0609
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	HCC827 (3×10⁶) cells suspended in 100 uL of PBS were injected into the left inguen of female Balb/c nude mice (body weight 18-20 g; age 6 weeks; Beijing Huafukang Bioscience Co., Inc.). When the tumor volumes reached 50-100 mm³ on the 10th posttransplantation day, the mice were randomized into four groups (10 mice per group) and were intragastrically administered vehicle (normal saline), crizotinib (25 mg/kg body weight), chidamide (5 mg/kg), or the combination of the two drugs daily for 21 days. The tumor volumes and body weights of the mice were measured every 3 days.
Response Summary	Chidamide could decrease Hepatocyte growth factor receptor (c-Met/MET) expression by inhibiting mRNA N6-methyladenosine (m6A) modification through the downregulation of METTL3 and WTAP expression, subsequently increasing the crizotinib sensitivity of NSCLC cells in a c-MET-/HGF-dependent manner.

Hexokinase-2 (HK2)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: WTAP-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -8.37E-01 p-value: 2.23E-65
More Results	Click to View More RNA-seq Results

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[9]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Target Regulation	Up regulation
Pathway Response	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glycolysis
In-vitro Model	SGC-7901	Gastric carcinoma	Homo sapiens	CVCL_0520
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	GES-1	Normal	Homo sapiens	CVCL_EQ22
	BGC-823	Gastric carcinoma	Homo sapiens	CVCL_3360
	AGS	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
Response Summary	Oncogenic role of WTAP and its m6A-mediated regulation on gastric cancer Warburg effect, providing a novel approach and therapeutic target in gastric cancer. WTAP enhanced the stability of Hexokinase-2 (HK2) mRNA through binding with the 3'-UTR m6A site.

LIM and SH3 domain protein 1 (LASP1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mice hepatocyte	Mus musculus
Treatment: Wtap Hknockout mice hepatocyte Control: Wtap flox/flox mice hepatocyte		GSE168850
Regulation		logFC: 9.34E-01 p-value: 1.43E-03
More Results	Click to View More RNA-seq Results

Nasopharyngeal carcinoma [ICD-11: 2B6B]

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	Nasopharyngeal carcinoma [ICD-11: 2B6B]
Target Regulation	Up regulation
Response Summary	WTAP-mediated m6A modification of LIM and SH3 domain protein 1 (LASP1) enhanced its stability relying on the m6A reader IGF2BP2-dependent pathway. Furthermore, DIAPH1-AS1 acted as a molecular adaptor that promoted MTDH-LASP1 complex formation and upregulated LASP1 expression, ultimately facilitating NPC growth and metastasis.

Myc proto-oncogene protein (MYC)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mice hepatocyte	Mus musculus
Treatment: Wtap Hknockout mice hepatocyte Control: Wtap flox/flox mice hepatocyte		GSE168850
Regulation		logFC: 2.89E+00 p-value: 1.82E-04
More Results	Click to View More RNA-seq Results

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				[11]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Responsed Drug	Daunorubicin		Approved	Drug Info
Target Regulation	Up regulation
Cell Process	Cell cycle
	Cell proliferation
	Cell apoptosis
In-vitro Model	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
Response Summary	WTAP made acute myeloid leukemia cells resistant to daunorubicin. In further investigations, m6A methylation level was downregulated when knocking down WTAP, and Myc proto-oncogene protein (MYC) was upregulated due to the decreased m6A methylation of MYC mRNA.

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

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mice hepatocyte	Mus musculus
Treatment: Wtap Hknockout mice hepatocyte Control: Wtap flox/flox mice hepatocyte		GSE168850
Regulation		logFC: 9.05E-01 p-value: 1.07E-04
More Results	Click to View More RNA-seq Results

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				[3]
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Pathway Response	NF-kappa B signaling pathway			hsa04064
	Apoptosis			hsa04210
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	Ishikawa	Endometrial adenocarcinoma	Homo sapiens	CVCL_2529
	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293
Response Summary	WTAP could methylate 3'-UTR of CAV-1 and downregulate CAV-1 expression to activate Nuclear factor NF-kappa-B p105 subunit (NF-Kappa-B/NFKB1) signaling pathway in EC, which promoted EC progression.

PI3-kinase subunit beta (PIK3CB)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mice hepatocyte	Mus musculus
Treatment: Wtap Hknockout mice hepatocyte Control: Wtap flox/flox mice hepatocyte		GSE168850
Regulation		logFC: 5.88E-01 p-value: 1.20E-03
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				[12]
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Responsed Drug	AZD6482		Terminated	Drug Info
Target Regulation	Up 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.

Protein C-ets-1 (ETS1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mice hepatocyte	Mus musculus
Treatment: Wtap Hknockout mice hepatocyte Control: Wtap flox/flox mice hepatocyte		GSE168850
Regulation		logFC: 1.11E+00 p-value: 3.10E-03
More Results	Click to View More RNA-seq Results

Liver cancer [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[13]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell proliferation and tumor growth
	Cell apoptosis
	Arrest cell cycle at G2/M phase
In-vitro Model	HCCLM3	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens	CVCL_0326
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0336
	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	PLC/PRF/5	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0485
	QSG-7701	Endocervical adenocarcinoma	Homo sapiens	CVCL_6944
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
In-vivo Model	3 × 10⁶ treated HCC cells resuspended in 100 uL PBS were subcutaneously injected to the left flank of the mice, which were randomly divided into several groups. Tumor sizes were measured every 3 to 5 days.
Response Summary	WTAP-guided m6A modification contributes to the progression of Hepatocellular carcinoma cells via the HuR-Protein C-ets-1 (ETS1)-p21/p27 axis.

Protein patched homolog 1 (PTCH1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: WTAP-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 1.15E+00 p-value: 6.91E-68
More Results	Click to View More RNA-seq Results

Hepatic fibrosis/cirrhosis [ICD-11: DB93]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene			[14]
Responsed Disease	Hepatic fibrosis [ICD-11: DB93.0]
Responsed Drug	AcSDKP	Phase 2	Drug Info
Target Regulation	Down regulation
Pathway Response	Hedgehog signaling pathway		hsa04340
Cell Process	Cell apoptosis
In-vitro Model	HSC (Hematopoietic stem cell)
In-vivo Model	Male Sprague-Dawley rats (375-400 g) liver fibrosis was induced by subcutaneous injection of carbon tetrachloride (CCl4) and olive oil (a ratio of 2:3) twice per week.
Response Summary	AcSDKP in liver fibrosis via m6A modification and Hedgehog pathway, which helps us to shed light on the molecular mechanism in liver fibrosis progression. WTAP targeted the 3'-UTR of Protein patched homolog 1 (PTCH1) mRNA, and administration of AcSDKP reduced the stability of Ptch1 mRNA.

Serine/threonine-protein kinase STK11 (STK11/LKB1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	CD4+ T cells	Mus musculus
Treatment: Wtap knockout CD4+ T cells Control: Wild type CD4+ T cells		GSE188814
Regulation		logFC: 1.01E+00 p-value: 6.29E-04
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				[2]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12.02]
Target Regulation	Up regulation
Pathway Response	AMPK signaling pathway			hsa04152
Pathway Response	Autophagy			hsa04140
Cell Process	Cell autophagy
In-vitro Model	BEL-7402	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
	BEL-7404	Endocervical adenocarcinoma	Homo sapiens	CVCL_6568
	HEK293T	Normal	Homo sapiens	CVCL_0063
	L-02	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	SMMC-7721	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
Response Summary	WTAP/Serine/threonine-protein kinase STK11 (STK11/LKB1)/AMPK axis in hepatocellular carcinoma cells acted as a key regulator, linking m6A with autophagy. WTAP-mediated m6A modification plays an important role in the regulation of autophagy in hepatocellular carcinoma cells, which provides a promising target for the treatment of hepatocellular carcinoma.

Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	Human umbilical vein endothelial cells	Homo sapiens
Treatment: siWTAP HUVECs Control: siControl HUVECs		GSE167067
Regulation		logFC: 1.73E+00 p-value: 1.15E-04
More Results	Click to View More RNA-seq Results

Rheumatoid arthritis [ICD-11: FA20]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[15]
Responsed Disease	Rheumatoid arthritis [ICD-11: FA20]
Pathway Response	JAK-STAT signaling pathway			hsa04630
	Cytokine-cytokine receptor interaction			hsa04060
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	MH7A	Normal	Homo sapiens	CVCL_0427
In-vivo Model	The rats were adaptively fed for 1 week and then subcutaneous injection of complete Freund's adjuvant into the left hindfoot toe to establish an adjuvant arthritis (AA) rat model. After induction of the immune response for 20 days, all rats were anesthetized by the intraperitoneal injection of 1% sodium pentobarbital (60 mg/kg) and sacrificed by exsanguination of the abdominal aorta.
Response Summary	This study established the transcriptional map of m6A in MH7A cells and revealed the potential relationship between RNA methylation modification and rheumatoid arthritis related genes. The results suggested that m6A modification was associated with the occurrence and course of RA to some extent. The validations of WTAP, RIPK2, JAK3 and Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A) were in accordance with the m6A and RNA sequencing results.

Tyrosine-protein kinase JAK3 (JAK3)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	Human umbilical vein endothelial cells	Homo sapiens
Treatment: siWTAP HUVECs Control: siControl HUVECs		GSE167067
Regulation		logFC: 1.47E+00 p-value: 6.40E-04
More Results	Click to View More RNA-seq Results

Rheumatoid arthritis [ICD-11: FA20]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[15]
Responsed Disease	Rheumatoid arthritis [ICD-11: FA20]
Pathway Response	JAK-STAT signaling pathway			hsa04630
	Cytokine-cytokine receptor interaction			hsa04060
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	MH7A	Normal	Homo sapiens	CVCL_0427
In-vivo Model	The rats were adaptively fed for 1 week and then subcutaneous injection of complete Freund's adjuvant into the left hindfoot toe to establish an adjuvant arthritis (AA) rat model. After induction of the immune response for 20 days, all rats were anesthetized by the intraperitoneal injection of 1% sodium pentobarbital (60 mg/kg) and sacrificed by exsanguination of the abdominal aorta.
Response Summary	This study established the transcriptional map of m6A in MH7A cells and revealed the potential relationship between RNA methylation modification and rheumatoid arthritis related genes. The results suggested that m6A modification was associated with the occurrence and course of RA to some extent. The validations of WTAP, RIPK2, Tyrosine-protein kinase JAK3 (JAK3) and TNFRSF10A were in accordance with the m6A and RNA sequencing results.

Long intergenic non-protein coding RNA 657 (NORAD)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	Human umbilical vein endothelial cells	Homo sapiens
Treatment: siWTAP HUVECs Control: siControl HUVECs		GSE167067
Regulation		logFC: -7.45E-01 p-value: 4.90E-04
More Results	Click to View More RNA-seq Results

Intervertebral disc degeneration [ICD-11: FA80]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[16]
Responsed Disease	Intervertebral disc degeneration [ICD-11: FA80]
Pathway Response	Cellular senescence	hsa04218
Cell Process	Cell senescence
In-vitro Model	Nucleus pulposus cells (NPCs) (Nucleus pulposus cells)
In-vivo Model	After 50g male NORAD-KO or C57 mice at age of 8 weeks were anesthetized with 3% (w/v) pentobarbital (2 ml/kg) and grouped randomly, investigators blinded to the group allocation performed the experiment. The disc levels in rat tail (Co6/7, 7/8, and 8/9) were located by palpation on the coccygeal vertebrae and confirmed by trial radiography. Needles (33-G) were used to puncture the annulus fibrosus layer though the tail skin, in parallel to the end plates. To ensure that the needle did not penetrate too deeply , the length of the needle was pre-determined according to the dimensions of annulus fibrosus and the NP , which were measured in a preliminary experiment and found to be approximately 4 mm. Five kinds of solution were prepared for intradisc injection, including AA V vector, AAV containing shPUM1, AAV containing shPUM2 for Norad KO mice, AAV vector, AAV containing shE2F3, AAVcontaining OE-E2F3 for WT mice.
Response Summary	Subsequent loss- and gain-of-function experiments reveal WTAP is increased in senescent nucleus pulposus cells, and significantly promotes Long intergenic non-protein coding RNA 657 (NORAD) m6A modification. This study shows interruption of NORAD m6A modification or the NORAD/PUMILIO/E2F3 axis could serve as a potential therapeutic target to inhibit the senescence of NPCs and development of intervertebral disc degeneration(IVDD).

Homeobox-containing protein 1 (HMBOX1)

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				[17]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	U2OS	Osteosarcoma	Homo sapiens	CVCL_0042
	SJSA-1	Osteosarcoma	Homo sapiens	CVCL_1697
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	HOS	Osteosarcoma	Homo sapiens	CVCL_0312
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
	143B	Osteosarcoma	Homo sapiens	CVCL_2270
In-vivo Model	Nude mice (4 weeks, male) were used for tumor model.For the subcutaneous tumor model, 1 × 10⁶ shNC, shWTAP or shHMBOX1 or shWTAP/shHMBOX1 U2OS cells seeded into mice via subcutaneous injection. Tumor volume and tumor weight were measured to analyze tumor growth as previous described. For orthotopic xenograft tumor model, shNC, shWTAP, shHMBOX1, or shWTAP/shHMBOX1 U2OS cells were labeled with a luminescent dye and GFP, and injected into the cavity of the tibia of mice. Thirty days after injection, tumor growth was detected. For the metastasis model, the cells were injected into the tail vein, and the lung metastasis were detected 30 days after injection using in vivo bioluminescence imaging system.
Response Summary	Homeobox-containing protein 1 (HMBOX1) was identified as the target gene of WTAP, WTAP/HMBOX1 regulated osteosarcoma growth and metastasis via PI3K/AKT pathway.

Mammalian target of rapamycin complex 2 (mTORC2)

Target Gene

Cerebrovascular diseases [ICD-11: 8B22]

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	Arteriovenous malformation of cerebral vessels [ICD-11: 8B22.40]
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
Response Summary	WTAP has been identified as a key subunit of the m6A methyltransferase complex, was down-regulated in brain arteriovenous malformations (AVMs) lesions.

Putative C->U-editing enzyme APOBEC-4 (APOBEC4)

Target Gene

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[19]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
In-vitro Model	HEY	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0297
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
Response Summary	Putative C->U-editing enzyme APOBEC-4 (APOBEC4) was found to be significantly correlated with m6A regulators such as WTAP, METTL14, ZC3H13, RBM15B, and FMR1. APOBEC3A was identified as a protective factor from comprehensive analyses based on the immune microenvironment and genomic instability of ovarian cancer. APOBEC3A had the potential to serve as a promising prognostic biomarker for foretelling the survival and immunotherapy response of ovarian cancer patients.

Receptor-interacting serine/threonine-protein kinase 2 (RIPK2)

Target Gene

Rheumatoid arthritis [ICD-11: FA20]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[15]
Responsed Disease	Rheumatoid arthritis [ICD-11: FA20]
Pathway Response	JAK-STAT signaling pathway			hsa04630
	Cytokine-cytokine receptor interaction			hsa04060
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	MH7A	Normal	Homo sapiens	CVCL_0427
In-vivo Model	The rats were adaptively fed for 1 week and then subcutaneous injection of complete Freund's adjuvant into the left hindfoot toe to establish an adjuvant arthritis (AA) rat model. After induction of the immune response for 20 days, all rats were anesthetized by the intraperitoneal injection of 1% sodium pentobarbital (60 mg/kg) and sacrificed by exsanguination of the abdominal aorta.
Response Summary	This study established the transcriptional map of m6A in MH7A cells and revealed the potential relationship between RNA methylation modification and rheumatoid arthritis related genes. The results suggested that m6A modification was associated with the occurrence and course of RA to some extent. The validations of WTAP, Receptor-interacting serine/threonine-protein kinase 2 (RIPK2), JAK3 and TNFRSF10A were in accordance with the m6A and RNA sequencing results.

DIAPH1 antisense RNA 1 (DIAPH1-AS1)

Target Gene

Nasopharyngeal carcinoma [ICD-11: 2B6B]

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	Nasopharyngeal carcinoma [ICD-11: 2B6B]
Target Regulation	Up regulation
Response Summary	WTAP-mediated m6A modification of DIAPH1 antisense RNA 1 (DIAPH1-AS1) enhanced its stability relying on the m6A reader IGF2BP2-dependent pathway. Furthermore, DIAPH1-AS1 acted as a molecular adaptor that promoted MTDH-LASP1 complex formation and upregulated LASP1 expression, ultimately facilitating NPC growth and metastasis.

DLGAP1 antisense RNA 1 (DLGAP1-AS1)

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				[20]
Responsed Disease	Breast cancer [ICD-11: 2C60]
Responsed Drug	Doxil		Approved	Drug Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
In-vitro Model	ADR-resistant MCF-7 (MCF-7/ADR) cells (Human breast cancer doxorubicin-resistant cell line)
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-10A	Normal	Homo sapiens	CVCL_0598
Response Summary	LncRNA DLGAP1-AS1 promotes BC ADR-resistance through WTAP/DLGAP1 antisense RNA 1 (DLGAP1-AS1)/miR-299-3p feedback loop in breast cancer.

FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1)

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				[7]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]
Target Regulation	Up regulation
In-vitro Model	SaOS-2	Osteosarcoma	Homo sapiens	CVCL_0548
	MG-63	Osteosarcoma	Homo sapiens	CVCL_0426
	hFOB 1.19	Normal	Homo sapiens	CVCL_3708
In-vivo Model	In vivo animal assay, FOXD2-AS1 overexpression promoted the tumor growth in mice subcutaneous injection
Response Summary	A remarkable m6A-modified site was found on the 3'-UTR of FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1), and m6A methyltransferase WTAP promoted the methylation modification, thus enhancing the stability of FOXD2-AS1 transcripts. m6A-modified FOXD2-AS1 accelerates the osteosarcoma progression through m6A manner, which provides new concepts for osteosarcoma tumorigenesis. FOXD2-AS1 interacted with downstream target FOXM1 mRNA through m6A sites, forming a FOXD2-AS1/m6A/FOXM1 complex to heighten FOXM1 mRNA stability.

hsa_circ_0008399

Target Gene

Bladder cancer [ICD-11: 2C94]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene				[21]
Responsed Disease	Bladder cancer [ICD-11: 2C94]
Responsed Drug	Cisplatin		Approved	Drug Info
Target Regulation	Up regulation
Pathway Response	Protein export			hsa03060
Cell Process	Eukaryotic translation
	Cell apoptosis
In-vitro Model	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
	RT-4	Bladder carcinoma	Homo sapiens	CVCL_0036
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
In-vivo Model	Chose 4-week-old female BALB/c nude mice for tumor xenograft experiments, which randomly were divided into four groups (n = 5 per group). Bladder cancer cells (3 × 10⁶) were subcutaneously injected into the right axilla of the nude mice.
Response Summary	Circ0008399 bound WTAP to promote formation of the WTAP/METTL3/METTL14 m6A methyltransferase complex, reduce cisplatin sensitivity in bladder cancer, implicating the potential therapeutic value of targeting this axis.

Unspecific 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				[23]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	Kasumi-1	Myeloid leukemia with maturation	Homo sapiens	CVCL_0589
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
Response Summary	microRNA 550a-1 mediated a decrease in m6A levels via targeting WTAP, which led to a further reduction in WWTR1 stability. Using gain- and loss-of-function approaches, we were able to determine that miR-550-1 disrupted the proliferation and tumorigenesis of acute myeloid leukemia cells at least in part via the direct targeting of WWTR1.

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene		[24]
Responsed Disease	Gastric cancer [ICD-11: 2B72]
Pathway Response	T cell receptor signaling pathway	hsa04660
Cell Process	Immunity
Response Summary	Wilms' tumour 1-associated protein was highly expressed in gastric cancer, which indicated a poor prognosis, and WTAP expression served as an independent predictor of GC survival. High WTAP expression correlated with RNA methylation and that low expression correlated with a high T cell-related immune response.

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				[25]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]
Cell Process	Cell apoptosis
In-vitro Model	CRL-11731D cell line (Human ovarian cancer cell)
	TOV-112D	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_3612
Response Summary	METTL3 can regulate m6A methylation independently of METTL14 and WTAP in endometrioid epithelial ovarian cancer.

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		[26]
Responsed Disease	Hematological disorders [ICD-11: 3C0Z]
Response Summary	This reviewed summarize and discuss recent findings regarding the biological functions and underlying mechanisms of m6A modification(i.e., the METTL3/METTL14/WTAP complex and other cofactor proteins) and the associated machinery in normal hematopoiesis and the initiation, progression, and drug response of acute myeloid leukemia (AML), a major subtype of leukemia usually associated with unfavorable prognosis.

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				[27]
Responsed Disease	Obesity [ICD-11: 5B81]
Cell Process	Adipogenesis
In-vitro Model	3T3F442A	Normal	Mus musculus	CVCL_0122
	3T3-L1	Normal	Mus musculus	CVCL_0123
	COS (From the African green monkey cell line (CV-1).)
	MEF (Mouse embryonic fibroblasts)
In-vivo Model	Mice were anesthetized after 24 h of fasting, and 5 U of human insulin (Humalin R; Eli Lilly) was injected into the inferior vena cava. After 5 min, the liver and hind limb muscles were dissected and immediately frozen in liquid nitrogen.
Response Summary	WTAP, coupled with METTL3 and METTL14, is increased and distributed in nucleus by the induction of adipogenesis dependently on RNA in vitro Knockdown of each of these three proteins leads to cell cycle arrest and impaired adipogenesis associated with suppression of cyclin A2 upregulation during MCE, whose knockdown also impairs adipogenesis.

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			[28]
Responsed Disease	Diseases of the circulatory system [ICD-11: BE2Z]
Responsed Drug	Sunitinib	Approved	Drug Info
In-vitro Model	hiPSCs (Urinary epithelial cell-derived hiPSCs)
	CMECs (Cardiac Microvascular Endothelial Cells )
	CFs (Cardiac Fibroblasts)
Response Summary	The RNA demethylase FTO was downregulated, whereas METTL14 and WTAP were upregulated. Furthermore, gain- and loss-of-function studies substantiated that FTO is cardioprotective in TKI(Sunitinib).

Dual specificity protein phosphatase 6 (DUSP6)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: WTAP-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -6.99E-01 p-value: 7.61E-15
More Results	Click to View More RNA-seq Results

Cisplatin [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[5]
Responsed Disease	Malignant haematopoietic neoplasm		ICD-11: 2B33	Disease Info
Target Regulation	Up regulation
Cell Process	Cell apoptosis
In-vitro Model	Normal NK cells (CD3-negative lymphocytes)
	SNK-6	Nasal type extranodal NK/T-cell lymphoma	Homo sapiens	CVCL_A673
	YTS	Lymphoblastic leukemia/lymphoma	Homo sapiens	CVCL_D324
Response Summary	m6A methyltransferase Wilms' tumor 1-associated protein facilitates cell proliferation and cisplatin resistance in NK/T cell lymphoma by regulating dual-specificity phosphatases 6 expression via m6A RNA methylation. WTAP enhanced Dual specificity protein phosphatase 6 (DUSP6) expression by increasing m6A levels of DUSP6 mRNA transcript, leading to oncogenic functions in NKTCL.

Focal adhesion kinase 1 (Fak)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: WTAP-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 5.98E-01 p-value: 1.29E-24
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				[6]
Responsed Disease	Pancreatic cancer		ICD-11: 2C10	Disease Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	RNA stability
In-vitro Model	T3M-4	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_4056
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	hTERT-HPNE	Normal	Homo sapiens	CVCL_C466
	HPDE6c7	Normal	Homo sapiens	CVCL_0P38
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
In-vivo Model	Twenty-four female BALB/c athymic nude mice, which were 4-6 weeks old and weighed 20.0-25.0 g, were obtained from the Animal Research Center of PUMCH. WTAP-OE, WTAP-NC, shWTAP and shNC-lentivirus infected MIA PaCa-2 cells (5 × 10⁶) were suspended in 50 uL PBS and then injected subcapsularly into the pancreatic tissue by 1-mL syringes.
Response Summary	WTAP could promote migration/invasion and suppress chemo-sensitivity to gemcitabine in PC. Further mechanical investigation revealed that WTAP could bind to and stabilize Focal adhesion kinase 1 (Fak) mRNA which in turn activated the Fak-PI3K-AKT and Fak-Src-GRB2-Erk1/2 signaling pathways.

Hepatocyte growth factor receptor (c-Met/MET)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: WTAP-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: -2.39E+00 p-value: 1.81E-38
More Results	Click to View More RNA-seq Results

Crizotinib [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[8]
Responsed Disease	Non-small-cell lung carcinoma		ICD-11: 2C25.Y	Disease Info
Target Regulation	Up regulation
Pathway Response	EGFR tyrosine kinase inhibitor resistance			hsa01521
In-vitro Model	HCC827	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	NCI-H661	Lung large cell carcinoma	Homo sapiens	CVCL_1577
	NCI-H596	Lung adenosquamous carcinoma	Homo sapiens	CVCL_1571
	NCI-H460	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H358	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1559
	NCI-H292	Lung mucoepidermoid carcinoma	Homo sapiens	CVCL_0455
	NCI-H1975	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	NCI-H1395	Lung adenocarcinoma	Homo sapiens	CVCL_1467
	EBC-1	Lung squamous cell carcinoma	Homo sapiens	CVCL_2891
	Calu-3	Lung adenocarcinoma	Homo sapiens	CVCL_0609
	A-549	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In-vivo Model	HCC827 (3×10⁶) cells suspended in 100 uL of PBS were injected into the left inguen of female Balb/c nude mice (body weight 18-20 g; age 6 weeks; Beijing Huafukang Bioscience Co., Inc.). When the tumor volumes reached 50-100 mm³ on the 10th posttransplantation day, the mice were randomized into four groups (10 mice per group) and were intragastrically administered vehicle (normal saline), crizotinib (25 mg/kg body weight), chidamide (5 mg/kg), or the combination of the two drugs daily for 21 days. The tumor volumes and body weights of the mice were measured every 3 days.
Response Summary	Chidamide could decrease Hepatocyte growth factor receptor (c-Met/MET) expression by inhibiting mRNA N6-methyladenosine (m6A) modification through the downregulation of METTL3 and WTAP expression, subsequently increasing the crizotinib sensitivity of NSCLC cells in a c-MET-/HGF-dependent manner.

Myc proto-oncogene protein (MYC)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mice hepatocyte	Mus musculus
Treatment: Wtap Hknockout mice hepatocyte Control: Wtap flox/flox mice hepatocyte		GSE168850
Regulation		logFC: 2.89E+00 p-value: 1.82E-04
More Results	Click to View More RNA-seq Results

Daunorubicin [Approved]

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	Acute myeloid leukaemia		ICD-11: 2A60	Disease Info
Target Regulation	Up regulation
Cell Process	Cell cycle
	Cell proliferation
	Cell apoptosis
In-vitro Model	K-562	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	MV4-11	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0064
Response Summary	WTAP made acute myeloid leukemia cells resistant to daunorubicin. In further investigations, m6A methylation level was downregulated when knocking down WTAP, and Myc proto-oncogene protein (MYC) was upregulated due to the decreased m6A methylation of MYC mRNA.

PI3-kinase subunit beta (PIK3CB)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mice hepatocyte	Mus musculus
Treatment: Wtap Hknockout mice hepatocyte Control: Wtap flox/flox mice hepatocyte		GSE168850
Regulation		logFC: 5.88E-01 p-value: 1.20E-03
More Results	Click to View More RNA-seq Results

AZD6482 [Terminated]

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	Pancreatic cancer		ICD-11: 2C10	Disease Info
Target Regulation	Up 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.

Protein patched homolog 1 (PTCH1)

Target Gene

*Representative RNA-seq result indicating the expression of this target gene regulated by WTAP*
Cell Line	mouse embryonic stem cells	Mus musculus
Treatment: WTAP-/- ESCs Control: Wild type ESCs		GSE145309
Regulation		logFC: 1.15E+00 p-value: 6.91E-68
More Results	Click to View More RNA-seq Results

AcSDKP [Phase 2]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[14]
Responsed Disease	Hepatic fibrosis	ICD-11: DB93.0	Disease Info
Target Regulation	Down regulation
Pathway Response	Hedgehog signaling pathway		hsa04340
Cell Process	Cell apoptosis
In-vitro Model	HSC (Hematopoietic stem cell)
In-vivo Model	Male Sprague-Dawley rats (375-400 g) liver fibrosis was induced by subcutaneous injection of carbon tetrachloride (CCl4) and olive oil (a ratio of 2:3) twice per week.
Response Summary	AcSDKP in liver fibrosis via m6A modification and Hedgehog pathway, which helps us to shed light on the molecular mechanism in liver fibrosis progression. WTAP targeted the 3'-UTR of Protein patched homolog 1 (PTCH1) mRNA, and administration of AcSDKP reduced the stability of Ptch1 mRNA.

DLGAP1 antisense RNA 1 (DLGAP1-AS1)

Target Gene

Doxil [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene				[20]
Responsed Disease	Breast cancer		ICD-11: 2C60	Disease Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
In-vitro Model	ADR-resistant MCF-7 (MCF-7/ADR) cells (Human breast cancer doxorubicin-resistant cell line)
	BT-549	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	MCF-7	Invasive breast carcinoma	Homo sapiens	CVCL_0031
	MDA-MB-231	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MCF-10A	Normal	Homo sapiens	CVCL_0598
Response Summary	LncRNA DLGAP1-AS1 promotes BC ADR-resistance through WTAP/DLGAP1 antisense RNA 1 (DLGAP1-AS1)/miR-299-3p feedback loop in breast cancer.

hsa_circ_0008399

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				[21]
Responsed Disease	Bladder cancer		ICD-11: 2C94	Disease Info
Target Regulation	Up regulation
Pathway Response	Protein export			hsa03060
Cell Process	Eukaryotic translation
Cell Process	Cell apoptosis
In-vitro Model	5637	Bladder carcinoma	Homo sapiens	CVCL_0126
	RT-4	Bladder carcinoma	Homo sapiens	CVCL_0036
	UM-UC-3	Bladder carcinoma	Homo sapiens	CVCL_1783
In-vivo Model	Chose 4-week-old female BALB/c nude mice for tumor xenograft experiments, which randomly were divided into four groups (n = 5 per group). Bladder cancer cells (3 × 10⁶) were subcutaneously injected into the right axilla of the nude mice.
Response Summary	Circ0008399 bound WTAP to promote formation of the WTAP/METTL3/METTL14 m6A methyltransferase complex, reduce cisplatin sensitivity in bladder cancer, implicating the potential therapeutic value of targeting this axis.

Unspecific Target Gene

Arsenite [Phase 2]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene		[22]
Cell Process	Cell apoptosis
In-vitro Model	HBE (Human bronchial epithelial cell line)
Response Summary	m6A modification on RNA was significantly increased in arsenite-transformed cells and this modification was synergistically regulated by METTL3, METTL14, WTAP and FTO. Demonstrated the significant role of m6A in the prevention of tumor occurrence and progression induced by arsenite.

Sunitinib [Approved]

In total 1 item(s) under this drug			Drug Info
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene			[28]
Responsed Disease	Diseases of the circulatory system	ICD-11: BE2Z	Disease Info
In-vitro Model	hiPSCs (Urinary epithelial cell-derived hiPSCs)
	CMECs (Cardiac Microvascular Endothelial Cells )
	CFs (Cardiac Fibroblasts)
Response Summary	The RNA demethylase FTO was downregulated, whereas METTL14 and WTAP were upregulated. Furthermore, gain- and loss-of-function studies substantiated that FTO is cardioprotective in TKI(Sunitinib).

Click to View Potential Drug Response of This Regulator

Xenobiotics Compound(s) Regulating the m6A Methylation Regulator

Compound Name	4-PBA	Phase 2
Synonyms	Benzenebutyric acid; Phenyl butanoate; Phenyl butyrate; HDInhib_000004; Butanoic acid, phenyl ester; Butyric acid, phenyl ester; FR-2080; Gamma-Phenylbutyric acid; Omega-Phenylbutanoic acid; GAMMA-PHENYL-BUTYRIC ACID; Butyric acid, 4-phenyl-(8CI); 1-Phenylbutyric acid; 4-PHENYL-BUTANOIC ACID; 4-PHENYLBUTYRIC ACID; 4-Phenylbutanoic acid; 4-phenylbutans; 4-phenylbutyrate Click to Show/Hide
External link	CID: 4775 TTD: D0B7CH DrugBank: DB06819
Description	Myocardial infarction (MI) is one of the leading causes of death. WTAP promoted myocardial I/R injury through promoting ER stress and cell apoptosis by regulating m6A modification ofATF4 mRNA. H/R effects on ER stress and apoptosis were all blocked by silencing of WTAP, promoted by WTAP overexpression, and ameliorated by administration of ER stress inhibitor, 4-PBA.	[4]
Compound Name	4-(dimethylamino)-N-[3-[[2-(4-oxochromen-7-yl)oxyacetyl]amino]phenyl]benzamide	Investigative
Synonyms	CHEMBL4438748; BDBM50519662 Click to Show/Hide
External link	CID: 155513187
Activity	IC50=3141 nM	[29]

References

Ref 1	C5aR1-positive neutrophils promote breast cancer glycolysis through WTAP-dependent m6A methylation of ENO1. Cell Death Dis. 2021 Jul 26;12(8):737. doi: 10.1038/s41419-021-04028-5.
Ref 2	m(6)A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK. Genes (Basel). 2021 Oct 30;12(11):1747. doi: 10.3390/genes12111747.
Ref 3	WTAP facilitates progression of endometrial cancer via CAV-1/NF-KappaB axis. Cell Biol Int. 2021 Jun;45(6):1269-1277. doi: 10.1002/cbin.11570. Epub 2021 Feb 19.
Ref 4	WTAP promotes myocardial ischemia/reperfusion injury by increasing endoplasmic reticulum stress via regulating m(6)A modification of ATF4 mRNA. Aging (Albany NY). 2021 Mar 26;13(8):11135-11149. doi: 10.18632/aging.202770. Epub 2021 Mar 26.
Ref 5	m6A methyltransferase Wilms' tumor 1-associated protein facilitates cell proliferation and cisplatin resistance in NK/T cell lymphoma by regulating dual-specificity phosphatases 6 expression via m6A RNA methylation. IUBMB Life. 2021 Jan;73(1):108-117. doi: 10.1002/iub.2410. Epub 2020 Nov 17.
Ref 6	WT1 associated protein promotes metastasis and chemo-resistance to gemcitabine by stabilizing Fak mRNA in pancreatic cancer. Cancer Lett. 2019 Jun 1;451:48-57. doi: 10.1016/j.canlet.2019.02.043. Epub 2019 Mar 6.
Ref 7	N(6)-methyladenosine methyltransferase WTAP-stabilized FOXD2-AS1 promotes the osteosarcoma progression through m(6)A/FOXM1 axis. Bioengineered. 2022 Apr;13(4):7963-7973. doi: 10.1080/21655979.2021.2008218.
Ref 8	Chidamide increases the sensitivity of Non-small Cell Lung Cancer to Crizotinib by decreasing c-MET mRNA methylation. Int J Biol Sci. 2020 Jul 19;16(14):2595-2611. doi: 10.7150/ijbs.45886. eCollection 2020.
Ref 9	N(6)-methyladenosine (m(6)A) methyltransferase WTAP accelerates the Warburg effect of gastric cancer through regulating HK2 stability. Biomed Pharmacother. 2021 Jan;133:111075. doi: 10.1016/j.biopha.2020.111075. Epub 2020 Dec 9.
Ref 10	WTAP-mediated m(6)A modification of lncRNA DIAPH1-AS1 enhances its stability to facilitate nasopharyngeal carcinoma growth and metastasis. Cell Death Differ. 2022 Jun;29(6):1137-1151. doi: 10.1038/s41418-021-00905-w. Epub 2022 Jan 8.
Ref 11	High Wilms' tumor 1 associating protein expression predicts poor prognosis in acute myeloid leukemia and regulates m(6)A methylation of MYC mRNA. J Cancer Res Clin Oncol. 2021 Jan;147(1):33-47. doi: 10.1007/s00432-020-03373-w. Epub 2020 Sep 3.
Ref 12	N(6)-methyladenosine mRNA methylation of PIK3CB regulates AKT signalling to promote PTEN-deficient pancreatic cancer progression. Gut. 2020 Dec;69(12):2180-2192. doi: 10.1136/gutjnl-2019-320179. Epub 2020 Apr 20.
Ref 13	WTAP facilitates progression of hepatocellular carcinoma via m6A-HuR-dependent epigenetic silencing of ETS1. Mol Cancer. 2019 Aug 22;18(1):127. doi: 10.1186/s12943-019-1053-8.
Ref 14	N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) mitigates the liver fibrosis via WTAP/m(6)A/Ptch1 axis through Hedgehog pathway. Gene. 2022 Mar 1;813:146125. doi: 10.1016/j.gene.2021.146125. Epub 2021 Dec 16.
Ref 15	Transcriptome-Wide High-Throughput m6A Sequencing of Differential m6A Methylation Patterns in the Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes Cell Line MH7A. J Inflamm Res. 2021 Feb 25;14:575-586. doi: 10.2147/JIR.S296006. eCollection 2021.
Ref 16	WTAP-mediated m(6)A modification of lncRNA NORAD promotes intervertebral disc degeneration. Nat Commun. 2022 Mar 18;13(1):1469. doi: 10.1038/s41467-022-28990-6.
Ref 17	WTAP promotes osteosarcoma tumorigenesis by repressing HMBOX1 expression in an m(6)A-dependent manner. Cell Death Dis. 2020 Aug 19;11(8):659. doi: 10.1038/s41419-020-02847-6.
Ref 18	Wilms' tumour 1-associating protein inhibits endothelial cell angiogenesis by m6A-dependent epigenetic silencing of desmoplakin in brain arteriovenous malformation. J Cell Mol Med. 2020 May;24(9):4981-4991. doi: 10.1111/jcmm.15101. Epub 2020 Apr 13.
Ref 19	Comprehensive Analyses Identify APOBEC3A as a Genomic Instability-Associated Immune Prognostic Biomarker in Ovarian Cancer. Front Immunol. 2021 Oct 21;12:749369. doi: 10.3389/fimmu.2021.749369. eCollection 2021.
Ref 20	N(6)-methyladenosine (m(6)A)-mediated lncRNA DLGAP1-AS1enhances breast canceradriamycin resistance through miR-299-3p/WTAP feedback loop. Bioengineered. 2021 Dec;12(2):10935-10944. doi: 10.1080/21655979.2021.2000198.
Ref 21	Circ0008399 Interaction with WTAP Promotes Assembly and Activity of the m(6)A Methyltransferase Complex and Promotes Cisplatin Resistance in Bladder Cancer. Cancer Res. 2021 Dec 15;81(24):6142-6156. doi: 10.1158/0008-5472.CAN-21-1518. Epub 2021 Oct 26.
Ref 22	N(6)-methyladenosine mediates the cellular proliferation and apoptosis via microRNAs in arsenite-transformed cells. Toxicol Lett. 2018 Aug;292:1-11. doi: 10.1016/j.toxlet.2018.04.018. Epub 2018 Apr 20.
Ref 23	miR-550-1 functions as a tumor suppressor in acute myeloid leukemia via the hippo signaling pathway. Int J Biol Sci. 2020 Sep 1;16(15):2853-2867. doi: 10.7150/ijbs.44365. eCollection 2020.
Ref 24	High expression of WTAP leads to poor prognosis of gastric cancer by influencing tumour-associated T lymphocyte infiltration. J Cell Mol Med. 2020 Apr;24(8):4452-4465. doi: 10.1111/jcmm.15104. Epub 2020 Mar 16.
Ref 25	METTL3 regulates m6A in endometrioid epithelial ovarian cancer independently of METTl14 and WTAP. Cell Biol Int. 2020 Dec;44(12):2524-2531. doi: 10.1002/cbin.11459. Epub 2020 Sep 11.
Ref 26	RNA N (6)-Methyladenosine Modification in Normal and Malignant Hematopoiesis. Adv Exp Med Biol. 2019;1143:75-93. doi: 10.1007/978-981-13-7342-8_4.
Ref 27	The RNA Methyltransferase Complex of WTAP, METTL3, and METTL14 Regulates Mitotic Clonal Expansion in Adipogenesis. Mol Cell Biol. 2018 Jul 30;38(16):e00116-18. doi: 10.1128/MCB.00116-18. Print 2018 Aug 15.
Ref 28	Alteration of N(6)-Methyladenosine mRNA Methylation in a Human Stem Cell-Derived Cardiomyocyte Model of Tyrosine Kinase Inhibitor-Induced Cardiotoxicity. Front Cardiovasc Med. 2022 Mar 23;9:849175. doi: 10.3389/fcvm.2022.849175. eCollection 2022.
Ref 29	Discovery of 4H-Chromen-4-one Derivatives as a New Class of Selective Rho Kinase (ROCK) Inhibitors, which Showed Potent Activity in ex Vivo Diabetic Retinopathy Models. J Med Chem. 2019 Dec 12;62(23):10691-10710. doi: 10.1021/acs.jmedchem.9b01143. Epub 2019 Nov 20.

m6A Regulator Information

Cite M6AREG

Correspondence

Prof. Feng ZHU

Prof. Shuiping Liu

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