METTL3-induced UCK2 m(6)A hypermethylation promotes melanoma cancer cell metastasis via the WNT/beta-catenin pathway

doi:10.21037/atm-21-2906

	METTL3-induced UCK2 m(6)A hypermethylation promotes melanoma cancer cell metastasis via the WNT/beta-catenin pathway
	Wu, Hao 1,2; Xu, Haochao 1,2; Jia, Dongdong 1,2; Li, Tao 1,2; Xia, Liming 1,2
刊名	ANNALS OF TRANSLATIONAL MEDICINE
	2021-07-13
关键词	Uridine-cytidine kinase 2 (UCK2) database m(6)A metastasis melanoma cancer
ISSN号	2305-5839
DOI	10.21037/atm-21-2906
通讯作者	Xia, Liming(doctorxlm@sina.com)
英文摘要	Background: Melanoma is a highly aggressive, malignant skin tumor with a statistically high mortality rate. N6-methyladenosine (m(6)A) modification is involved in a variety of biological processes, including tumorigenesis. m(6)A modifications regulate the fate and functions of RNA, such as mRNA stability, nuclear processing, transport, localization, translation, primary microRNA (miRNA) processing, and RNA-protein interactions. Several members (including METTL3, METTL14, FTO, ALKBH5, and YTHDF2) are actively involved in a variety of human cancers. However, the basic mechanism of the involvement of uridine cytidine kinase 2 (UCK2) in melanoma metastasis has not been studied. UCK2 is upregulated in a variety of malignancies. However, the complex molecular mechanisms and therapeutic effects of UCK2 in melanoma remain unclear. Methods: The expression of UCK2 was evaluated by qRT-PCR. The effects of UCK2 on the biological characteristics of PC cells were investigated on the basis of loss-of-function analyses. ImmunoprecipitationqPCR (MeRIP-qPCR) was performed to identify the m(6)A targeted effect of UCK2 in melanoma cancer. Results: Based on the bioinformatics analysis in this study, up-regulation of UCK2 could be essential in melanoma cancer, and associated with poor survival. Furthermore, the m(6)A modification regulated by METTL3 led to UCK2 increased messenger RNA (mRNA) stability in melanoma cancer. Functional and mechanistic experiments indicated that UCK2 enhanced the metastasis of melanoma cancer cells through the WNT/13-catenin pathway. Conclusion: In this study, we found that m(6)A-METTL3 axis induced abnormal UCK2 expression plays a role in melanoma metastasis by enhancing the Wnt/13-catenin pathway, which may provide new clues for melanoma metastasis. It also provides a potential target for the prevention and treatment of melanoma.
资助项目	Health Science and Technology program of Zhejiang Province[2021KY106]
WOS关键词	CYTIDINE KINASE 2 ; PROLIFERATION ; STATISTICS ; ACTIVATION ; EXPRESSION ; BIOMARKER ; INVASION ; ASSAY
WOS研究方向	Oncology ; Research & Experimental Medicine
语种	英语
出版者	AME PUBL CO
WOS记录号	WOS:000677657200001
资助机构	Health Science and Technology program of Zhejiang Province
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/123200]
专题	中国科学院合肥物质科学研究院
通讯作者	Xia, Liming
作者单位	1.Chinese Acad Sci, Inst Canc & Basic Med IBMC, Hangzhou, Peoples R China 2.Univ Chinese Acad Sci, Canc Hosp, Dept Bone & Soft Tissue Surg, Zhejiang Canc Hosp, Hangzhou, Peoples R China
推荐引用方式 GB/T 7714	Wu, Hao,Xu, Haochao,Jia, Dongdong,et al. METTL3-induced UCK2 m(6)A hypermethylation promotes melanoma cancer cell metastasis via the WNT/beta-catenin pathway[J]. ANNALS OF TRANSLATIONAL MEDICINE,2021.
APA	Wu, Hao,Xu, Haochao,Jia, Dongdong,Li, Tao,&Xia, Liming.(2021).METTL3-induced UCK2 m(6)A hypermethylation promotes melanoma cancer cell metastasis via the WNT/beta-catenin pathway.ANNALS OF TRANSLATIONAL MEDICINE.
MLA	Wu, Hao,et al."METTL3-induced UCK2 m(6)A hypermethylation promotes melanoma cancer cell metastasis via the WNT/beta-catenin pathway".ANNALS OF TRANSLATIONAL MEDICINE (2021).