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

Background Melanoma is a highly aggressive, malignant skin tumor with a statistically high mortality rate. N6-methyladenosine (m6A) modification is involved in a variety of biological processes, including tumorigenesis. m6A 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. Immunoprecipitation-qPCR (MeRIP-qPCR) was performed to identify the m6A 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 m6A 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/β-catenin pathway. Conclusion In this study, we found that m6A-METTL3 axis induced abnormal UCK2 expression plays a role in melanoma metastasis by enhancing the Wnt/β-catenin pathway, which may provide new clues for melanoma metastasis. It also provides a potential target for the prevention and treatment of melanoma.