Name	Endometrial cancer
ICD	ICD-11: 2C76

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
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.
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulator	Wilms tumor 1-associating protein (WTAP)		WRITER	Regulator Info
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

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	knocking down METTL5 could significantly activate apoptosis and inhibit endometrial carcinoma(EC) development via MMR administration.METTL5 expression in UCEC tumor tissue was increased, and UCEC patients with high METTL5 expression had worse prognostic outcomes. METTL5 knockdown induced the DNA mismatch repair protein Msh2 (MSH2), MSH6 and PMS2 expression in MMR.
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulator	Methyltransferase-like 5 (METTL5)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Mismatch repair			hsa03430
Cell Process	DNA mismatch repair
	Microsatellite instability
In-vitro Model	CP-H058 (Normal endometrial cells)
	KLE	Endometrial adenocarcinoma	Homo sapiens	CVCL_1329
	RL95-2	Endometrial adenosquamous carcinoma	Homo sapiens	CVCL_0505
	Ishikawa	Endometrial adenocarcinoma	Homo sapiens	CVCL_2529
	ECC-1	Endometrial Cancer	Homo sapiens	CVCL_7260
In-vivo Model	The male BALB/c nude mice were randomized divide into two groups, each group including six 4 weeks old nude mice. Investigators were blinded to the treatment groups during data collection and subsequent data analysis. In the subcutaneous xenograft model, 5 × 105 cells were subcutaneously injected in the right flanks of nude mice. In the orthotopic intracranial mouse model, each mouse was intracranially injected with 1 × 105 luciferase transfected U87MG cells in 10 uL PBS solution.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	knocking down METTL5 could significantly activate apoptosis and inhibit endometrial carcinoma(EC) development via MMR administration.METTL5 expression in UCEC tumor tissue was increased, and UCEC patients with high METTL5 expression had worse prognostic outcomes. METTL5 knockdown induced the MSH2, DNA mismatch repair protein Msh6 (MSH6) and PMS2 expression in MMR.
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulator	Methyltransferase-like 5 (METTL5)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Mismatch repair			hsa03430
Cell Process	DNA mismatch repair
	Microsatellite instability
In-vitro Model	CP-H058 (Normal endometrial cells)
	KLE	Endometrial adenocarcinoma	Homo sapiens	CVCL_1329
	RL95-2	Endometrial adenosquamous carcinoma	Homo sapiens	CVCL_0505
	Ishikawa	Endometrial adenocarcinoma	Homo sapiens	CVCL_2529
	ECC-1	Endometrial Cancer	Homo sapiens	CVCL_7260
In-vivo Model	The male BALB/c nude mice were randomized divide into two groups, each group including six 4 weeks old nude mice. Investigators were blinded to the treatment groups during data collection and subsequent data analysis. In the subcutaneous xenograft model, 5 × 105 cells were subcutaneously injected in the right flanks of nude mice. In the orthotopic intracranial mouse model, each mouse was intracranially injected with 1 × 105 luciferase transfected U87MG cells in 10 uL PBS solution.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	This study found high expression of FTO in metastatic endometrial cancer and that this action promote both metastasis and invasion in vivo and in vitro. Mechanistically, FTO can catalyse demethylation modification in 3'UTR region of Homeobox protein Hox-B13 (HOXB13) mRNA, thereby abolishing m6A modification recognition with the YTHDF2 protein.
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Wnt signaling pathway			hsa04310
In-vitro Model	KLE	Endometrial adenocarcinoma	Homo sapiens	CVCL_1329
	AN3-CA	Endometrial adenocarcinoma	Homo sapiens	CVCL_0028
In-vivo Model	Female SCID-Beige mice (6 weeks old) were purchased from Vitalriver. AN3CA cells with FTO overexpression or silencing or the appropriate controls (1 × 106) were injected into the lower abdominal cavity of mice (n = 5 mice/group). After 4 weeks, the mice were sacrificed, and tumours were harvested, weighed and photographed.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	YTHDF2 inhibited the proliferation and invasion of endometrial cancer(EC) via inhibiting Insulin receptor substrate 1 (IRS1) expression in m6A epigenetic way, which suggests a potential therapeutic target for EC.
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
In-vitro Model	T HESCs	Normal	Homo sapiens	CVCL_C464
	RL95-2	Endometrial adenosquamous carcinoma	Homo sapiens	CVCL_0505
	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	ALKBH5 promoted proliferation and invasion of endometrial cancer via erasing Insulin-like growth factor 1 receptor (IGF1R) m6A-modifications
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	T HESCs	Normal	Homo sapiens	CVCL_C464
	RL95-2	Endometrial adenosquamous carcinoma	Homo sapiens	CVCL_0505
	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	About 70% of endometrial tumours exhibit reductions in m6A methylation that are probably due to either this METTL14 mutation or reduced expression of METTL3. Reductions in m6A methylation lead to decreased expression of the negative AKT regulator PHLPP2 and increased expression of the positive AKT regulator Mammalian target of rapamycin complex 2 (mTORC2). these results reveal reduced m6A mRNA methylation as an oncogenic mechanism in endometrial cancer and identify m6A methylation as a regulator of AKT signalling.
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Cell Process	Cell proliferation and tumorigenicity
In-vitro Model	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293
	RL95-2	Endometrial adenosquamous carcinoma	Homo sapiens	CVCL_0505
	T HESCs	Normal	Homo sapiens	CVCL_C464
In-vivo Model	4×106 HEC-1-A endometrial cancer cells (shCtrl, shMETTL3, wild-type, METTL14+/-, or METTL14+/- rescued with wild-type or mutant METTL14) were injected intraperitoneally into 5 week old female athymic nude mice (Foxn1nu, Harlan; n=10 per group).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	About 70% of endometrial tumours exhibit reductions in m6A methylation that are probably due to either this METTL14 mutation or reduced expression of METTL3. Reductions in m6A methylation lead to decreased expression of the negative AKT regulator PHLPP2 and increased expression of the positive AKT regulator Mammalian target of rapamycin complex 2 (mTORC2). these results reveal reduced m6A mRNA methylation as an oncogenic mechanism in endometrial cancer and identify m6A methylation as a regulator of AKT signalling.
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293
In-vivo Model	4×106 HEC-1-A endometrial cancer cells (shCtrl, shMETTL3, wild-type, METTL14+/-, or METTL14+/- rescued with wild-type or mutant METTL14) were injected intraperitoneally into 5 week old female athymic nude mice (Foxn1nu, Harlan; n=10 per group).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	knocking down METTL5 could significantly activate apoptosis and inhibit endometrial carcinoma(EC) development via MMR administration.METTL5 expression in UCEC tumor tissue was increased, and UCEC patients with high METTL5 expression had worse prognostic outcomes. METTL5 knockdown induced the MSH2, MSH6 and Mismatch repair endonuclease PMS2 (PMS2) expression in MMR.
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulator	Methyltransferase-like 5 (METTL5)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Mismatch repair			hsa03430
Cell Process	DNA mismatch repair
	Microsatellite instability
In-vitro Model	CP-H058 (Normal endometrial cells)
	KLE	Endometrial adenocarcinoma	Homo sapiens	CVCL_1329
	RL95-2	Endometrial adenosquamous carcinoma	Homo sapiens	CVCL_0505
	Ishikawa	Endometrial adenocarcinoma	Homo sapiens	CVCL_2529
	ECC-1	Endometrial Cancer	Homo sapiens	CVCL_7260
In-vivo Model	The male BALB/c nude mice were randomized divide into two groups, each group including six 4 weeks old nude mice. Investigators were blinded to the treatment groups during data collection and subsequent data analysis. In the subcutaneous xenograft model, 5 × 105 cells were subcutaneously injected in the right flanks of nude mice. In the orthotopic intracranial mouse model, each mouse was intracranially injected with 1 × 105 luciferase transfected U87MG cells in 10 uL PBS solution.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
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.
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulator	Wilms tumor 1-associating protein (WTAP)		WRITER	Regulator Info
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

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	About 70% of endometrial tumours exhibit reductions in m6A methylation that are probably due to either this METTL14 mutation or reduced expression of METTL3. Reductions in m6A methylation lead to decreased expression of the negative AKT regulator PHLPP-like (PHLPP2) and increased expression of the positive AKT regulator mTORC2. these results reveal reduced m6A mRNA methylation as an oncogenic mechanism in endometrial cancer and identify m6A methylation as a regulator of AKT signalling.
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation and tumorigenicity
In-vitro Model	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293
	RL95-2	Endometrial adenosquamous carcinoma	Homo sapiens	CVCL_0505
	T HESCs	Normal	Homo sapiens	CVCL_C464
In-vivo Model	4×106 HEC-1-A endometrial cancer cells (shCtrl, shMETTL3, wild-type, METTL14+/-, or METTL14+/- rescued with wild-type or mutant METTL14) were injected intraperitoneally into 5 week old female athymic nude mice (Foxn1nu, Harlan; n=10 per group).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	About 70% of endometrial tumours exhibit reductions in m6A methylation that are probably due to either this METTL14 mutation or reduced expression of METTL3. Reductions in m6A methylation lead to decreased expression of the negative AKT regulator PHLPP-like (PHLPP2) and increased expression of the positive AKT regulator mTORC2. these results reveal reduced m6A mRNA methylation as an oncogenic mechanism in endometrial cancer and identify m6A methylation as a regulator of AKT signalling.
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell proliferation and tumorigenicity
In-vitro Model	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293
	RL95-2	Endometrial adenosquamous carcinoma	Homo sapiens	CVCL_0505
	T HESCs	Normal	Homo sapiens	CVCL_C464
In-vivo Model	4×106 HEC-1-A endometrial cancer cells (shCtrl, shMETTL3, wild-type, METTL14+/-, or METTL14+/- rescued with wild-type or mutant METTL14) were injected intraperitoneally into 5 week old female athymic nude mice (Foxn1nu, Harlan; n=10 per group).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	IGF2BP1 expression increased in EC, and high expression of this protein correlated with poor prognosis. IGF2BP1 can recognize m6A sites in the 3'UTR of PEG10 mRNA and recruits PABPC1 to enhance Retrotransposon-derived protein PEG10 (PEG10) mRNA stability, which consequently promotes PEG10 protein expression.
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	RL95-2	Endometrial adenosquamous carcinoma	Homo sapiens	CVCL_0505
	KLE	Endometrial adenocarcinoma	Homo sapiens	CVCL_1329
	Ishikawa	Endometrial adenocarcinoma	Homo sapiens	CVCL_2529
	HEC-1-B	Endometrial adenocarcinoma	Homo sapiens	CVCL_0294
	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293
	AN3-CA	Endometrial adenocarcinoma	Homo sapiens	CVCL_0028
In-vivo Model	Six-week-old, female SCID-Berge mice were purchased from Vitalriver. EC cells with IGF2BP1 overexpression or silencing or the appropriate controls (1×106) were injected into lower abdominal cavity of each mouse (n = 5 mice/group).

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	HIF-dependent ALKBH5 expression increases in hypoxic TMEs, resulting in the demethylation of Transcription factor SOX-2 (SOX2) mRNA and the maintenance of the Endometrial cancer stem cells phenotype; these data indicate that ECSCs maintain their stemness by activating the HIF/ALKBH5/SOX2 axis under hypoxic conditions.
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	HIF-1 signaling pathway			hsa04066
	Signaling pathways regulating pluripotency of stem cells			hsa04550
In-vitro Model	EC cell line (Primary EC cells)
	HEC-1-A	Endometrial adenocarcinoma	Homo sapiens	CVCL_0293
	Ishikawa	Endometrial adenocarcinoma	Homo sapiens	CVCL_2529
	RL95-2	Endometrial adenosquamous carcinoma	Homo sapiens	CVCL_0505
In-vivo Model	A method of randomisation was used to determine the experimental groups. In total, 78 female BALB/c nu/nu mice (4-6-week-old) were selected at random and were divided into different groups. A total of 5 × 106 ISK cells or 1 × 104 ECSCisk were suspended in 100 uL of PBS and then were injected into the mice. After 2 weeks, the presence of tumours was examined. ISK cells (5 × 106, 5 × 105, 5 × 104, 1 × 104, or 1 × 103) and ECSCisk (1 × 104, 1 × 103, 1 × 102, 10, or 1) were injected and analysed for their abilities to form xenograft tumours. After 4 weeks, subsequent experiments were performed.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[9]
Response Summary	Dysregulation of IGF2BP1 by PADI2/MEK1/ERK signaling results in abnormal accumulation of oncogenic Transcription factor SOX-2 (SOX2) expression, therefore supporting the malignant state of EC.
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	RNA stability
In-vitro Model	Ishikawa	Endometrial adenocarcinoma	Homo sapiens	CVCL_2529
	ECC-1	Endometrial Cancer	Homo sapiens	CVCL_7260
In-vivo Model	Nude mice were subcutaneously injected with 1 × 107 PADI2 depleted or IGF2BP1 depleted Ishikawa cells on the left flanks, and the corresponding control cells on the right flanks.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[10]
Response Summary	YTHDF2-mediated LncRNA FENDRR degradation promotes cell proliferation by elevating Transcription factor SOX-4 (SOX4) expression in endometrioid endometrial carcinoma.
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	HEC-1-B	Endometrial adenocarcinoma	Homo sapiens	CVCL_0294

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[10]
Response Summary	YTHDF2-mediated LncRNA FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) degradation promotes cell proliferation by elevating SOX4 expression in endometrioid endometrial carcinoma.
Responsed Disease	Endometrial cancer [ICD-11: 2C76]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Cell Process	Cell proliferation
	Cell apoptosis
In-vitro Model	HEC-1-B	Endometrial adenocarcinoma	Homo sapiens	CVCL_0294

Ref 1	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 2	The potential role of methyltransferase-like 5 in deficient mismatch repair of uterine corpus endometrial carcinoma. Bioengineered. 2022 Mar;13(3):5525-5536. doi: 10.1080/21655979.2022.2036912.
Ref 3	FTO demethylates m6A modifications in HOXB13 mRNA and promotes endometrial cancer metastasis by activating the WNT signalling pathway. RNA Biol. 2021 Sep;18(9):1265-1278. doi: 10.1080/15476286.2020.1841458. Epub 2020 Nov 5.
Ref 4	YTHDF2 inhibit the tumorigenicity of endometrial cancer via downregulating the expression of IRS1 methylated with m(6)A. J Cancer. 2021 May 5;12(13):3809-3818. doi: 10.7150/jca.54527. eCollection 2021.
Ref 5	ALKBH5 regulates IGF1R expression to promote the Proliferation and Tumorigenicity of Endometrial Cancer. J Cancer. 2020 Jul 25;11(19):5612-5622. doi: 10.7150/jca.46097. eCollection 2020.
Ref 6	m(6)A mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer. Nat Cell Biol. 2018 Sep;20(9):1074-1083. doi: 10.1038/s41556-018-0174-4. Epub 2018 Aug 27.
Ref 7	IGF2BP1 overexpression stabilizes PEG10 mRNA in an m6A-dependent manner and promotes endometrial cancer progression. Theranostics. 2021 Jan 1;11(3):1100-1114. doi: 10.7150/thno.49345. eCollection 2021.
Ref 8	Hypoxia induces an endometrial cancer stem-like cell phenotype via HIF-dependent demethylation of SOX2 mRNA. Oncogenesis. 2020 Sep 11;9(9):81. doi: 10.1038/s41389-020-00265-z.
Ref 9	PADI2-Catalyzed MEK1 Citrullination Activates ERK1/2 and Promotes IGF2BP1-Mediated SOX2 mRNA Stability in Endometrial Cancer. Adv Sci (Weinh). 2021 Jan 29;8(6):2002831. doi: 10.1002/advs.202002831. eCollection 2021 Mar.
Ref 10	N-methyladenosine reader YTHDF2-mediated long noncoding RNA FENDRR degradation promotes cell proliferation in endometrioid endometrial carcinoma. Lab Invest. 2021 Jun;101(6):775-784. doi: 10.1038/s41374-021-00543-3. Epub 2021 Mar 10.