Name	Esophageal cancer
ICD	ICD-11: 2B70

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	The levels of m6A and its regulator HNRNPA2B1 were significantly increased in cancerous tissues of esophageal cancer(ESCA), and overexpression of HNRNPA2B1 promotes ESCA progression via up-regulation of de novo fatty acid synthetic enzymes ACLY and Acetyl-CoA carboxylase 1 (ACC1/ACACA).
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Metabolic pathways			hsa01100
Cell Process	Fatty acid synthesis
In-vitro Model	TE-10	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1760
	Eca-109	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	m6A-RNA immunoprecipitation sequencing revealed that METTL3 upregulates the m6A modification of Adenomatous polyposis coli protein (APC), which recruits YTHDF for APC mRNA degradation. Our findings reveal a mechanism by which the Wnt/Bete-catenin pathway is upregulated in ESCC via METTL3/YTHDF-coupled epitranscriptomal downregulation of APC.
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Wnt signaling pathway			hsa04310
	Cell cycle			hsa04110
	Glycolysis / Gluconeogenesis			hsa00010
Cell Process	Glycolysis
In-vitro Model	TE-10	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1760
	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
	KYSE-70	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1356
	KYSE-450	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1353
	KYSE-410	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1352
	KYSE-30	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1351
	KYSE-180	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1349
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
	KYSE-140	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1347
	HET-1A	Normal	Homo sapiens	CVCL_3702
In-vivo Model	For the subcutaneous implantation model, 1 × 106 cells were injected subcutaneously into the flank regions of female BALB/c nude mice (4-5 weeks).

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	The levels of m6A and its regulator HNRNPA2B1 were significantly increased in cancerous tissues of esophageal cancer(ESCA), and overexpression of HNRNPA2B1 promotes ESCA progression via up-regulation of de novo fatty acid synthetic enzymes ATP-citrate synthase (ACLY) and ACC1.
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Target Regulator	Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Metabolic pathways			hsa01100
Cell Process	Fatty acid synthesis
In-vitro Model	TE-10	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1760
	Eca-109	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	FTO relys on the reading protein YTHDF1 to affect the translation pathway of the Estradiol 17-beta-dehydrogenase 11 (HSD17B11) gene to regulate the formation of lipid droplets in esophageal cancer cells.
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Cell Process	Lipid metabolism
In-vitro Model	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
	KYSE-510	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1354
In-vivo Model	Nude mice were randomly divided into five groups of six mice each, and the mice in each group were received subcutaneous injections of shFTO, scrambled shNC, FTO OE, and vector KYSE510 cells (5×106 tumor cells/mouse), respectively. The tumor size and weight of mice were measured 1 week later, which was recorded as day 0, and then measured once every other day; and the tumor volumes were calculated using the following formula: (length×width2)/2.When the tumor maximum diameter was close to 15 mm, the mice were euthanized and the tumor tissues were collected for immunohistochemistry analysis.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	METTL3 plays a carcinogenic role in human EC progression partially through RAC-alpha serine/threonine-protein kinase (AKT1) signaling pathways, suggesting that METTL3 serves as a potential therapeutic target for esophageal cancer therapy. A double-effect inhibitor (BEZ235) inhibited AKT and mTOR phosphorylation and hindered the effect of METTL3 overexpression on the proliferation and migration of Eca-109 and KY-SE150 cells.
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	PI3K-Akt signaling pathway			hsa04151
	Wnt signaling pathway			hsa04310
	mTOR signaling pathway			hsa04150
	Apoptosis			hsa04210
Cell Process	Cell proliferation and invasion
	Cell apoptosis
In-vitro Model	Eca-109	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
	Normal esophageal epithelial cell line (HEEC) (Isolated from the human esophagus)

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 demethylated pri-miR-194-2 and inhibited miR-194-2 biogenesis through an m6A/DGCR8-dependent manner. ALKBH5/miR-194-2/Retinoic acid-induced protein 1 (RAI1) axis was also validated in clinical samples. This study revealed ALKBH5 in miRNAs biogenesis and provide novel insight for developing treatment strategies in esophageal cancer.
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Down regulation

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	Platinum can increase the overall m6A level of esophageal cancer. Small nucleolar RNA host gene 3 (SNHG3)/miR-186-5p, induced by platinum, was involved in regulating m6A level by targeting METTL3. miR-186-5p binds to the 3'UTR of METTL3 to inhibit its expression. Our manuscript has provided clues that regulating m6A level was a novel way to enhance the platinum efficacy.
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Responsed Drug	Pt		Investigative	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cellular Processes
	Cell growth and death
	Cell apoptosis
In-vitro Model	Eca-9706 (Esophageal carcinoma cell line)
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
In-vivo Model	Used 1 × 106 SNHG3 knocked down KY-SE150 cells and NC lentivirus to inject into the right flank of mice to generate xenografts.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	HNRNPC, YTHDF, ZC3H13, YTHDC2, and METTL14 were dysregulated in esophageal cancer tissues. miR-186 interacted with HNRNPC and suppressed the expression of HNRNPC. Four miRNAs (microRNA 186 (MIR186), miR-320c, miR-320d, and miR-320b) were used to construct a prognostic signature, which could serve as a prognostic predictor independent from routine clinicopathological features.
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Target Regulator	Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC)		READER	Regulator Info
In-vitro Model	HEEC cell line (Normal esophageal epithelial cell line)
	KYSE-30	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1351
	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759

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 demethylated pri-miR-194-2 and inhibited miR-194-2 biogenesis through an m6A/DGCR8-dependent manner. ALKBH5/miR-194-2/RAI1 axis was also validated in clinical samples. This study revealed ALKBH5 in miRNAs biogenesis and provide novel insight for developing treatment strategies in esophageal cancer.
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Down regulation

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	Platinum can increase the overall m6A level of esophageal cancer. SNHG3/hsa-miR-186-5p, induced by platinum, was involved in regulating m6A level by targeting METTL3. miR-186-5p binds to the 3'UTR of METTL3 to inhibit its expression. Our manuscript has provided clues that regulating m6A level was a novel way to enhance the platinum efficacy.
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Responsed Drug	Pt		Investigative	Drug Info
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cellular Processes
	Cell growth and death
	Cell apoptosis
In-vitro Model	Eca-9706 (Esophageal carcinoma cell line)
	KYSE-150	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1348
In-vivo Model	Used 1 × 106 SNHG3 knocked down KY-SE150 cells and NC lentivirus to inject into the right flank of mice to generate xenografts.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	HNRNPC, YTHDF, ZC3H13, YTHDC2, and METTL14 were dysregulated in esophageal cancer tissues. miR-186 interacted with HNRNPC and suppressed the expression of HNRNPC. Four miRNAs (miR-186, miR-320c, miR-320d, and hsa-miR-320b) were used to construct a prognostic signature, which could serve as a prognostic predictor independent from routine clinicopathological features.
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Target Regulator	Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC)		READER	Regulator Info
In-vitro Model	HEEC cell line (Normal esophageal epithelial cell line)
	KYSE-30	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1351
	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	HNRNPC, YTHDF, ZC3H13, YTHDC2, and METTL14 were dysregulated in esophageal cancer tissues. miR-186 interacted with HNRNPC and suppressed the expression of HNRNPC. Four miRNAs (miR-186, hsa-miR-320c, miR-320d, and miR-320b) were used to construct a prognostic signature, which could serve as a prognostic predictor independent from routine clinicopathological features.
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Target Regulator	Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC)		READER	Regulator Info
In-vitro Model	HEEC cell line (Normal esophageal epithelial cell line)
	KYSE-30	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1351
	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	HNRNPC, YTHDF, ZC3H13, YTHDC2, and METTL14 were dysregulated in esophageal cancer tissues. miR-186 interacted with HNRNPC and suppressed the expression of HNRNPC. Four miRNAs (miR-186, miR-320c, hsa-miR-320d, and miR-320b) were used to construct a prognostic signature, which could serve as a prognostic predictor independent from routine clinicopathological features.
Responsed Disease	Esophageal cancer [ICD-11: 2B70]
Target Regulator	Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC)		READER	Regulator Info
In-vitro Model	HEEC cell line (Normal esophageal epithelial cell line)
	KYSE-30	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1351
	TE-1	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759

Ref 1	m(6)A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1. Front Oncol. 2020 Sep 29;10:553045. doi: 10.3389/fonc.2020.553045. eCollection 2020.
Ref 2	METTL3 promotes tumour development by decreasing APC expression mediated by APC mRNA N(6)-methyladenosine-dependent YTHDF binding. Nat Commun. 2021 Jun 21;12(1):3803. doi: 10.1038/s41467-021-23501-5.
Ref 3	m6A demethylase FTO promotes tumor progression via regulation of lipid metabolism in esophageal cancer. Cell Biosci. 2022 May 14;12(1):60. doi: 10.1186/s13578-022-00798-3.
Ref 4	METTL3 promotes the proliferation and invasion of esophageal cancer cells partly through AKT signaling pathway. Pathol Res Pract. 2020 Sep;216(9):153087. doi: 10.1016/j.prp.2020.153087. Epub 2020 Jun 27.
Ref 5	N(6)-methyladenosine demethylase ALKBH5 suppresses malignancy of esophageal cancer by regulating microRNA biogenesis and RAI1 expression. Oncogene. 2021 Sep;40(37):5600-5612. doi: 10.1038/s41388-021-01966-4. Epub 2021 Jul 26.
Ref 6	Targeting SNHG3/miR-186-5p reverses the increased m6A level caused by platinum treatment through regulating METTL3 in esophageal cancer. Cancer Cell Int. 2021 Feb 17;21(1):114. doi: 10.1186/s12935-021-01747-9.
Ref 7	Network analysis of miRNA targeting m6A-related genes in patients with esophageal cancer. PeerJ. 2021 Jul 29;9:e11893. doi: 10.7717/peerj.11893. eCollection 2021.