m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00005)

Target Name	Mammalian target of rapamycin complex 2 (mTORC2)
Uniprot ID	SIN1_HUMAN, LST8_HUMAN, MTOR_HUMAN, PRR5_HUMAN, RICTR_HUMAN

Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)

Mammalian target of rapamycin complex 2 (mTORC2) 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).

Browse Regulator

Browse Disease

Browse Drug

Fat mass and obesity-associated protein (FTO) [ERASER]

Regulator Info

In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene				[1]
Response Summary	FTO regulates pathological ocular angiogenesis by controlling endothelial cell function in an m6A-YTHDF2-dependent manner. Pathological ocular angiogenesis commonly results in visual impairment or even blindness.
Responsed Disease	Vision impairment		ICD-11: 9D90	Disease Info
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
In-vivo Model	After general anesthesia with an intraperitoneal injection of ketamine (80 mg/kg) and xylazine (4 mg/kg), topical application of 0.5% proparacaine ophthalmic solution was conducted. Three sutures (10-0 nylon) were placed intrastromally between the limbus and corneal center at the 4, 8, and 12 o'clock positions. Topical norfloxacin was applied after surgery.

Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) [READER]

Regulator Info

In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene				[2]
Response Summary	NNK is a Group 1 human carcinogen, as classified by the International Agency for Research of Cancer (IARC), and plays a significant role in lung carcinogenesis. However IGF2BP1 is involved in the NNK-induced malignant transformation of Beas-2B cells, via m6A modification.
Responsed Disease	Lung cancer		ICD-11: 2C25	Disease Info
Pathway Response	Chemical carcinogenesis - DNA adducts			hsa05204
Cell Process	Malignant transformation
In-vitro Model	BEAS-2B	Normal	Homo sapiens	CVCL_0168
In-vivo Model	Twenty 5-week-old male nude mice were randomly divided into two groups and injected with either 2B-NNK or 2B-C cells. Tumor growth was measured every 3 days.

Methyltransferase-like 14 (METTL14) [WRITER]

Regulator Info

In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene				[3]
Response Summary	Suppression of METTL14 obviously increased the sensitivity of gemcitabine in resistant cells. This study suggested that METTL14 is a potential target for chemotherapy resistance in pancreatic cancer.
Responsed Disease	Pancreatic cancer		ICD-11: 2C10	Disease Info
Responsed Drug	Gemcitabine		Approved	Drug Info
In-vitro Model	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	Hs 766T	Pancreatic adenocarcinoma	Homo sapiens	CVCL_0334
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
	Capan-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0026
In-vivo Model	NOD/SCID mice (6-week-old) were injected (subcutaneously in both flanks) with 5.0 x 10⁶ PANC-1 GemR cells (infected with scr or METTL14 shRNA) per mouse suspended in 50 ul PBS and mixed with equal volume of growth factor reduced matrigel. One week after injection, we started measuring tumor size at the indicated times. Tumor size was calculated by 0.5 × (long diameter) × (short diameter)2. The mice were treated with vehicle or 100 mg/kg gemcitabine intraperitoneally twice a week.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene				[4]
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.
Target Regulation	Down regulation
Responsed Disease	Endometrial cancer		ICD-11: 2C76	Disease Info
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 (Foxn1^nu, Harlan; n=10 per group).

Methyltransferase-like 3 (METTL3) [WRITER]

Regulator Info

In total 6 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene				[5]
Response Summary	HGHF-induced ferroptosis in osteoblasts is the main cause of osteoporosis in diabetes mellitus (DM) via activation of METTL3/ASK1-p38 signaling pathway, and inhibition of ferroptosis in osteoblasts provide a potential therapeutic strategy for diabetic osteoporosis.
In-vitro Model	MC3T3-E1	Normal	Mus musculus	CVCL_0409
In-vivo Model	Using the diabetic rat model established by HGHF feeding with a subsequent intraperitoneal injection of a single low dose of streptozocin.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene				[6]
Response Summary	The expression level of METTL3 positively correlated with molecular markers and infiltration level of CD8+ and CD4+ T cells and natural killer cells. In sum, These findings identified that METTL3 can be used as an independent prognostic marker in patients with testicular germ cell tumors (TGCTs).
Cell Process	Epithelial-mesenchymal transition, cell proliferation, cell migration, cell invasion
In-vitro Model	NCC-IT	Testicular embryonal carcinoma	Homo sapiens	CVCL_1451
In-vitro Model	TCam-2	Testicular seminoma	Homo sapiens	CVCL_T012
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene				[7]
Response Summary	METTL3 knockdown suppressed the HSV-1 intermediate early and early genes (ICP0, ICP8 and UL23) and late genes (VP16, UL44, UL49 and ICP47). The components of m6A modification machinery, particularly m6A initiator METTL3 and reader YTHDF3, would be potential important targets for combating herpes virus type 1 (HSV-1) infections.
Responsed Disease	Herpes infection		ICD-11: 1F00	Disease Info
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
In-vitro Model	RD	Embryonal rhabdomyosarcoma	Homo sapiens	CVCL_1649
Experiment 4 Reporting the m6A Methylation Regulator of This Target Gene				[4]
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.
Target Regulation	Down regulation
Responsed Disease	Endometrial cancer		ICD-11: 2C76	Disease Info
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 (Foxn1^nu, Harlan; n=10 per group).
Experiment 5 Reporting the m6A Methylation Regulator of This Target Gene				[8]
Response Summary	The expression level of METTL3 was reduced in the larger pathological tissues of cerebral arteriovenous malformation (AVM). Moreover, knockdown of METTL3 significantly affected angiogenesis of the human endothelial cells.
Responsed Disease	Arteriovenous malformation of cerebral vessels		ICD-11: 8B22.40	Disease Info
Pathway Response	Notch signaling pathway			hsa04330
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
Experiment 6 Reporting the m6A Methylation Regulator of This Target Gene				[9]
Response Summary	METTL3 knockout in vivo decreased avascular area and pathological neovascular tufts in an oxygen-induced retinopathy model and inhibited alkali burn-induced corneal neovascularization.
Responsed Disease	Retinopathy		ICD-11: 9B71	Disease Info
Cell Process	Cell viability
	Cell proliferation
	Cell migration
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
In-vivo Model	Mettl3^flox/flox mice were crossed with the transgenic Cdh5-CreERT2 mice to generate the Mettl3-ecKO mice. Cdh5-Cre Mettl3^flox/flox mice received an intragastric injection of 50 ul tamoxifen (1 mg/mL) at P1-P3 and P5 for Cre activation and Mettl3 knockout. After Mettl3 knockout, the mouse pups and their nursing mothers were exposed to 75% oxygen (hyperoxia) from P7 to P12 in an incubator chamber. Then, the pups were returned to normal oxygen conditions (normoxia).

RNA demethylase ALKBH5 (ALKBH5) [ERASER]

Regulator Info

In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene				[10]
Response Summary	ALKBH5 as a demethylase was lowly expressed in cancer progression of esophageal squamous cell carcinoma (ESCC) and acts as a crucial component in ESCC progression.
Responsed Disease	Esophageal squamous cell carcinoma		ICD-11: 2B70.1	Disease Info
Cell Process	Cell proliferation and invasion
In-vitro Model	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
In-vitro Model	Eca-109	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene				[11]
Response Summary	Functionally, the overexpression of ALKBH5 promoted apoptosis and inhibited the proliferation of T cells. ALKBH5 expression is downregulated in systemic lupus erythematosus (SLE) patients and could affect the apoptosis and proliferation of T cells.
Responsed Disease	Lupus erythematosus		ICD-11: 4A40	Disease Info
In-vitro Model	PBMCs (Human peripheral blood mononuclear cells (PBMCs) are isolated from peripheral blood and identified as any blood cell with a round nucleus)

RNA-binding motif protein 15 (RBM15) [WRITER]

Regulator Info

In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene				[12]
Response Summary	Knockdown of RBM15 remarkably suppressed the expression levels of multitarget genes related to programmed cell death and inflammatory response. These findings indicate that RBM15 can serve as a target for the treatment of COVID-19.
Responsed Disease	COVID-19		ICD-11: RA01	Disease Info
Cell Process	Programmed cell death
	Inflammatory response
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	HuT 78	T lymphocytic leukemia	Homo sapiens	CVCL_0337

Wilms tumor 1-associating protein (WTAP) [WRITER]

Regulator Info

In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene				[13]
Response Summary	WTAP has been identified as a key subunit of the m6A methyltransferase complex, was down-regulated in brain arteriovenous malformations (AVMs) lesions.
Responsed Disease	Arteriovenous malformation of cerebral vessels		ICD-11: 8B22.40	Disease Info
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959

YTH domain-containing family protein 1 (YTHDF1) [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	YTHDF1-promoted cisplatin resistance, contributing to overcoming chemoresistant colon cancers.
Responsed Disease	Colon cancer		ICD-11: 2B90	Disease Info
Responsed Drug	Cisplatin		Approved	Drug Info
Pathway Response	Metabolic pathways			hsa01100
Cell Process	Glutamine metabolism
In-vitro Model	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT-29	Colon adenocarcinoma	Homo sapiens	CVCL_0320
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	CRL-1790 (The normal colon epithelial cell line CRL-1790, were purchased from the American Type Culture Collection (ATCC).)
In-vivo Model	Mice were injected subcutaneously with LoVo (1 × 10⁶) cells, which were stably transfected with the control shRNA or YTHDF1 shRNA.

Herpes infection [ICD-11: 1F00]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response				[7]
Response Summary	METTL3 knockdown suppressed the HSV-1 intermediate early and early genes (ICP0, ICP8 and UL23) and late genes (VP16, UL44, UL49 and ICP47). The components of m6A modification machinery, particularly m6A initiator METTL3 and reader YTHDF3, would be potential important targets for combating herpes virus type 1 (HSV-1) infections.
Responsed Disease	Herpes infection [ICD-11: 1F00]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
In-vitro Model	HeLa	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
In-vitro Model	RD	Embryonal rhabdomyosarcoma	Homo sapiens	CVCL_1649

Colon cancer [ICD-11: 2B90]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response				[14]
Response Summary	YTHDF1-promoted cisplatin resistance, contributing to overcoming chemoresistant colon cancers.
Responsed Disease	Colon cancer [ICD-11: 2B90]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Responsed Drug	Cisplatin		Approved	Drug Info
Pathway Response	Metabolic pathways			hsa01100
Cell Process	Glutamine metabolism
In-vitro Model	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT-29	Colon adenocarcinoma	Homo sapiens	CVCL_0320
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	CRL-1790 (The normal colon epithelial cell line CRL-1790, were purchased from the American Type Culture Collection (ATCC).)
In-vivo Model	Mice were injected subcutaneously with LoVo (1 × 10⁶) cells, which were stably transfected with the control shRNA or YTHDF1 shRNA.

Pancreatic cancer [ICD-11: 2C10]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response				[3]
Response Summary	Suppression of METTL14 obviously increased the sensitivity of gemcitabine in resistant cells. This study suggested that METTL14 is a potential target for chemotherapy resistance in pancreatic cancer.
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Responsed Drug	Gemcitabine		Approved	Drug Info
In-vitro Model	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	Hs 766T	Pancreatic adenocarcinoma	Homo sapiens	CVCL_0334
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
	Capan-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0026
In-vivo Model	NOD/SCID mice (6-week-old) were injected (subcutaneously in both flanks) with 5.0 x 10⁶ PANC-1 GemR cells (infected with scr or METTL14 shRNA) per mouse suspended in 50 ul PBS and mixed with equal volume of growth factor reduced matrigel. One week after injection, we started measuring tumor size at the indicated times. Tumor size was calculated by 0.5 × (long diameter) × (short diameter)2. The mice were treated with vehicle or 100 mg/kg gemcitabine intraperitoneally twice a week.

Lung cancer [ICD-11: 2C25]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response				[2]
Response Summary	NNK is a Group 1 human carcinogen, as classified by the International Agency for Research of Cancer (IARC), and plays a significant role in lung carcinogenesis. However IGF2BP1 is involved in the NNK-induced malignant transformation of Beas-2B cells, via m6A modification.
Responsed Disease	Lung cancer [ICD-11: 2C25]
Target Regulator	Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)		READER	Regulator Info
Pathway Response	Chemical carcinogenesis - DNA adducts			hsa05204
Cell Process	Malignant transformation
In-vitro Model	BEAS-2B	Normal	Homo sapiens	CVCL_0168
In-vivo Model	Twenty 5-week-old male nude mice were randomly divided into two groups and injected with either 2B-NNK or 2B-C cells. Tumor growth was measured every 3 days.

Endometrial cancer [ICD-11: 2C76]

Disease Info

In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response				[4]
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 (Foxn1^nu, Harlan; n=10 per group).
Experiment 2 Reporting the m6A-centered Disease Response				[4]
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 (Foxn1^nu, Harlan; n=10 per group).

Oral cavity/oesophagus/stomach in situ carcinoma [ICD-11: 2E60]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response				[10]
Response Summary	ALKBH5 as a demethylase was lowly expressed in cancer progression of esophageal squamous cell carcinoma (ESCC) and acts as a crucial component in ESCC progression.
Responsed Disease	Esophageal squamous cell carcinoma [ICD-11: 2B70.1]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Cell Process	Cell proliferation and invasion
In-vitro Model	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
In-vitro Model	Eca-109	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898

Lupus erythematosus [ICD-11: 4A40]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response			[11]
Response Summary	Functionally, the overexpression of ALKBH5 promoted apoptosis and inhibited the proliferation of T cells. ALKBH5 expression is downregulated in systemic lupus erythematosus (SLE) patients and could affect the apoptosis and proliferation of T cells.
Responsed Disease	Lupus erythematosus [ICD-11: 4A40]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)	ERASER	Regulator Info
In-vitro Model	PBMCs (Human peripheral blood mononuclear cells (PBMCs) are isolated from peripheral blood and identified as any blood cell with a round nucleus)

Cerebrovascular diseases [ICD-11: 8B22]

Disease Info

In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response				[8]
Response Summary	The expression level of METTL3 was reduced in the larger pathological tissues of cerebral arteriovenous malformation (AVM). Moreover, knockdown of METTL3 significantly affected angiogenesis of the human endothelial cells.
Responsed Disease	Arteriovenous malformation of cerebral vessels [ICD-11: 8B22.40]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Pathway Response	Notch signaling pathway			hsa04330
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
Experiment 2 Reporting the m6A-centered Disease Response				[13]
Response Summary	WTAP has been identified as a key subunit of the m6A methyltransferase complex, was down-regulated in brain arteriovenous malformations (AVMs) lesions.
Responsed Disease	Arteriovenous malformation of cerebral vessels [ICD-11: 8B22.40]
Target Regulator	Wilms tumor 1-associating protein (WTAP)		WRITER	Regulator Info
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959

Retinopathy [ICD-11: 9B71]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response				[9]
Response Summary	METTL3 knockout in vivo decreased avascular area and pathological neovascular tufts in an oxygen-induced retinopathy model and inhibited alkali burn-induced corneal neovascularization.
Responsed Disease	Retinopathy [ICD-11: 9B71]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Cell Process	Cell viability
	Cell proliferation
	Cell migration
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
In-vivo Model	Mettl3^flox/flox mice were crossed with the transgenic Cdh5-CreERT2 mice to generate the Mettl3-ecKO mice. Cdh5-Cre Mettl3^flox/flox mice received an intragastric injection of 50 ul tamoxifen (1 mg/mL) at P1-P3 and P5 for Cre activation and Mettl3 knockout. After Mettl3 knockout, the mouse pups and their nursing mothers were exposed to 75% oxygen (hyperoxia) from P7 to P12 in an incubator chamber. Then, the pups were returned to normal oxygen conditions (normoxia).

Visual impairment [ICD-11: 9D90]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response				[1]
Response Summary	FTO regulates pathological ocular angiogenesis by controlling endothelial cell function in an m6A-YTHDF2-dependent manner. Pathological ocular angiogenesis commonly results in visual impairment or even blindness.
Responsed Disease	Vision impairment [ICD-11: 9D90]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
In-vitro Model	HUVEC-C	Normal	Homo sapiens	CVCL_2959
In-vivo Model	After general anesthesia with an intraperitoneal injection of ketamine (80 mg/kg) and xylazine (4 mg/kg), topical application of 0.5% proparacaine ophthalmic solution was conducted. Three sutures (10-0 nylon) were placed intrastromally between the limbus and corneal center at the 4, 8, and 12 o'clock positions. Topical norfloxacin was applied after surgery.

COVID-19 [ICD-11: RA01]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response				[12]
Response Summary	Knockdown of RBM15 remarkably suppressed the expression levels of multitarget genes related to programmed cell death and inflammatory response. These findings indicate that RBM15 can serve as a target for the treatment of COVID-19.
Responsed Disease	COVID-19 [ICD-11: RA01]
Target Regulator	RNA-binding motif protein 15 (RBM15)		WRITER	Regulator Info
Cell Process	Programmed cell death
	Inflammatory response
In-vitro Model	THP-1	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	HuT 78	T lymphocytic leukemia	Homo sapiens	CVCL_0337

Cisplatin [Approved]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response				[14]
Response Summary	YTHDF1-promoted cisplatin resistance, contributing to overcoming chemoresistant colon cancers.
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Responsed Disease	Colon cancer		ICD-11: 2B90	Disease Info
Pathway Response	Metabolic pathways			hsa01100
Cell Process	Glutamine metabolism
In-vitro Model	LoVo	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	HT-29	Colon adenocarcinoma	Homo sapiens	CVCL_0320
	DLD-1	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	CRL-1790 (The normal colon epithelial cell line CRL-1790, were purchased from the American Type Culture Collection (ATCC).)
In-vivo Model	Mice were injected subcutaneously with LoVo (1 × 10⁶) cells, which were stably transfected with the control shRNA or YTHDF1 shRNA.

Gemcitabine [Approved]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response				[3]
Response Summary	Suppression of METTL14 obviously increased the sensitivity of gemcitabine in resistant cells. This study suggested that METTL14 is a potential target for chemotherapy resistance in pancreatic cancer.
Target Regulator	Methyltransferase-like 14 (METTL14)		WRITER	Regulator Info
Responsed Disease	Pancreatic cancer		ICD-11: 2C10	Disease Info
In-vitro Model	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0428
	Hs 766T	Pancreatic adenocarcinoma	Homo sapiens	CVCL_0334
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0152
	Capan-2	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0026
In-vivo Model	NOD/SCID mice (6-week-old) were injected (subcutaneously in both flanks) with 5.0 x 10⁶ PANC-1 GemR cells (infected with scr or METTL14 shRNA) per mouse suspended in 50 ul PBS and mixed with equal volume of growth factor reduced matrigel. One week after injection, we started measuring tumor size at the indicated times. Tumor size was calculated by 0.5 × (long diameter) × (short diameter)2. The mice were treated with vehicle or 100 mg/kg gemcitabine intraperitoneally twice a week.

References

Ref 1	FTO regulates ocular angiogenesis via m(6)A-YTHDF2-dependent mechanism. Exp Eye Res. 2020 Aug;197:108107. doi: 10.1016/j.exer.2020.108107. Epub 2020 Jun 9.
Ref 2	Involvement of m6A regulatory factor IGF2BP1 in malignant transformation of human bronchial epithelial Beas-2B cells induced by tobacco carcinogen NNK. Toxicol Appl Pharmacol. 2022 Feb 1;436:115849. doi: 10.1016/j.taap.2021.115849. Epub 2021 Dec 30.
Ref 3	m(6)A Methyltransferase METTL14-Mediated Upregulation of Cytidine Deaminase Promoting Gemcitabine Resistance in Pancreatic Cancer. Front Oncol. 2021 Aug 11;11:696371. doi: 10.3389/fonc.2021.696371. eCollection 2021.
Ref 4	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 5	Activation of osteoblast ferroptosis via the METTL3/ASK1-p38 signaling pathway in high glucose and high fat (HGHF)-induced diabetic bone loss. FASEB J. 2022 Mar;36(3):e22147. doi: 10.1096/fj.202101610R.
Ref 6	METTL3 May Regulate Testicular Germ Cell Tumors Through EMT and Immune Pathways. Cell Transplant. 2020 Jan-Dec;29:963689720946653. doi: 10.1177/0963689720946653.
Ref 7	Targeting m6A modification inhibits herpes virus 1 infection. Genes Dis. 2021 Feb 22;9(4):1114-1128. doi: 10.1016/j.gendis.2021.02.004. eCollection 2022 Jul.
Ref 8	N6-methyladenosine methyltransferase METTL3 affects the phenotype of cerebral arteriovenous malformation via modulating Notch signaling pathway. J Biomed Sci. 2020 May 9;27(1):62. doi: 10.1186/s12929-020-00655-w.
Ref 9	Role of METTL3-Dependent N(6)-Methyladenosine mRNA Modification in the Promotion of Angiogenesis. Mol Ther. 2020 Oct 7;28(10):2191-2202. doi: 10.1016/j.ymthe.2020.07.022. Epub 2020 Jul 25.
Ref 10	ALKBH5 Is Lowly Expressed in Esophageal Squamous Cell Carcinoma and Inhibits the Malignant Proliferation and Invasion of Tumor Cells. Comput Math Methods Med. 2021 Nov 28;2021:1001446. doi: 10.1155/2021/1001446. eCollection 2021.
Ref 11	Down-regulated ALKBH5 Expression Could Affect the Function of T Cells in Systemic Lupus Erythematosus Patients. Curr Pharm Des. 2022 Jun 17. doi: 10.2174/1381612828666220617154204. Online ahead of print.
Ref 12	RBM15-mediated N6-methyladenosine modification affects COVID-19 severity by regulating the expression of multitarget genes. Cell Death Dis. 2021 Jul 23;12(8):732. doi: 10.1038/s41419-021-04012-z.
Ref 13	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 14	Targeting YTHDF1 effectively re-sensitizes cisplatin-resistant colon cancer cells by modulating GLS-mediated glutamine metabolism. Mol Ther Oncolytics. 2021 Jan 16;20:228-239. doi: 10.1016/j.omto.2021.01.001. eCollection 2021 Mar 26.

m6A Target Gene Information

Cite M6AREG

Correspondence

Prof. Feng ZHU

Prof. Shuiping Liu

Visitor Map