Name	Melanoma of uvea
ICD	ICD-11: 2D0Y

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	Beta-site APP-cleaving enzyme 2 (BACE2) presented an increased level of N6-methyladenosine (m6A) RNA methylation, which led to the upregulation of BACE2 mRNA. This study provides a novel pattern of BACE2-mediated intracellular calcium release in ocular melanoma progression.
Responsed Disease	Melanoma of uvea [ICD-11: 2D0Y]
Cell Process	Intracellular calcium release
In-vitro Model	MuM-2B	Uveal melanoma	Homo sapiens	CVCL_3447
	OM431	Uveal melanoma	Homo sapiens	CVCL_J308
	Mel290	Uveal melanoma	Homo sapiens	CVCL_C304
	OMM-1	Uveal melanoma	Homo sapiens	CVCL_6939
	()
	CRMM-1	Conjunctival melanoma	Homo sapiens	CVCL_M593
	CRMM-2	Conjunctival melanoma	Homo sapiens	CVCL_M594
	CM2005.1	Conjunctival melanoma	Homo sapiens	CVCL_M592
	HEK293T	Normal	Homo sapiens	CVCL_0063

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	YTHDF3 enhances Catenin beta-1 (CTNNB1/Beta-catenin) translation through recognizing and binding the m6A peaks on CTNNB1 mRNA.m6A reading protein YTHDF3 promotes the translation of the target transcript CTNNB1, contributing to ocular melanoma propagation and migration through m6A methylation.
Responsed Disease	Melanoma of uvea [ICD-11: 2D0Y]
Target Regulator	YTH domain-containing family protein 3 (YTHDF3)		READER	Regulator Info
Target Regulation	Up regulation

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	AKLBH5-induced m6A demethylation of Forkhead box protein M1 (FOXM1) mRNA promotes uveal melanoma progression.
Responsed Disease	Melanoma of uvea [ICD-11: 2D0Y]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Cell apoptosis
In-vitro Model	ARPE-19	Normal	Homo sapiens	CVCL_0145
	C918	Uveal melanoma	Homo sapiens	CVCL_8471
	MuM-2B	Uveal melanoma	Homo sapiens	CVCL_3447
In-vivo Model	The in vivo experiment method for transplantation of tumors was subcutaneous injection of 1 × 107 ALKBH5-stable knockdown C918 cells into BALB/c nude mice.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	METTL3-mediated m6A RNA methylation modulates uveal melanoma cell proliferation, migration, and invasion by targeting Hepatocyte growth factor receptor (c-Met/MET). Cycloleucine (Cyc) was used to block m6 A methylation in UM cells.
Responsed Disease	Melanoma of uvea [ICD-11: 2D0Y]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell proliferation
	Cell migration
	Cell invasion
	Arrest cell cycle at G1 phase
In-vitro Model	M17 (Neuroblastoma cells)
	M21	Melanoma	Homo sapiens	CVCL_D031
	M23	Cutaneous melanoma	Homo sapiens	CVCL_RT32
	SP-6.5	Uveal melanoma	Homo sapiens	CVCL_7997

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	m6A RNA methylation regulators take a crucial role in the potential malignant progression and prognostic value of uveal melanoma and were regarded as a new promising biomarker for UM prognosis and treatment strategy development. The malignant hallmarks of Mammalian target of rapamycin complex 1 (mTORC1) signaling, oxidative phosphorylation, interferon-a response and apoptosis signaling are also significantly enriched in the C1 subtype.
Responsed Disease	Melanoma of uvea [ICD-11: 2D0Y]
Pathway Response	mTOR signaling pathway			hsa04150
Cell Process	Oxidative phosphorylation
	Cell apoptosis

Ref 1	m(6)A RNA hypermethylation-induced BACE2 boosts intracellular calcium release and accelerates tumorigenesis of ocular melanoma. Mol Ther. 2021 Jun 2;29(6):2121-2133. doi: 10.1016/j.ymthe.2021.02.014. Epub 2021 Feb 15.
Ref 2	The m(6)A reading protein YTHDF3 potentiates tumorigenicity of cancer stem-like cells in ocular melanoma through facilitating CTNNB1 translation. Oncogene. 2022 Feb;41(9):1281-1297. doi: 10.1038/s41388-021-02146-0. Epub 2022 Feb 3.
Ref 3	Effects of S-2474, a novel nonsteroidal anti-inflammatory drug, on amyloid beta protein-induced neuronal cell death. Br J Pharmacol. 2001 Oct;134(3):673-81. doi: 10.1038/sj.bjp.0704261.
Ref 4	ALKBH5-mediated m(6)A demethylation of FOXM1 mRNA promotes progression of uveal melanoma. Aging (Albany NY). 2021 Jan 10;13(3):4045-4062. doi: 10.18632/aging.202371. Epub 2021 Jan 10.
Ref 5	RNA m(6) A methylation regulates uveal melanoma cell proliferation, migration, and invasion by targeting c-Met. J Cell Physiol. 2020 Oct;235(10):7107-7119. doi: 10.1002/jcp.29608. Epub 2020 Feb 4.
Ref 6	The prognostic values of m6A RNA methylation regulators in uveal melanoma. BMC Cancer. 2020 Jul 18;20(1):674. doi: 10.1186/s12885-020-07159-8.
Ref 7	4-(4-cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamides as selective cyclooxygenase-2 inhibitors: enhancement of the selectivity by introduction of a fluorine atom and identification of a potent, highly selective, and orally active COX-2 inhibitor JTE-522(1). J Med Chem. 2002 Mar 28;45(7):1511-7. doi: 10.1021/jm010484p.
Ref 8	Clinical pipeline report, company report or official report of BeiGene.