ALKBH5 facilitates the progression of skin cutaneous melanoma via mediating ABCA1 demethylation and modulating autophagy in an m 6 A-dependent manner

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Background: N6-methyladenosine (m 6 A) is the most common and abundant mRNA modification, playing an essential role in biological processes and tumor development.However, the role of m 6 A methylation in skin cutaneous melanoma (SKCM) is not yet clear.This study analyzed the expression of m 6 A-related functional genes in SKCM and aimed to explore the key demethylase ALKBH5 mediated m 6 A modification and its potential mechanism in human SKCM.Methods: Based on public databases, the m 6 A-related gene expression landscape in SKCM was portrayed.MeRIP-Seq and RNA-Seq were used to recognize the downstream target of ALKBH5.In vivo and in vitro functional phenotype and rescue functional experiments were performed to explore the mechanism of the ALKBH5-m 6 A-ABCA1 axis in SKCM.Results: We found ALKBH5 upregulated in SKCM, associated with poor prognosis.ALKBH5 can promote melanoma cell proliferation, colony formation, migration, and invasion and inhibit autophagy in vitro, facilitating tumor growth and metastasis in vivo.We identified ABCA1, a membrane protein that assists cholesterol efflux, as a downstream target of ALKBH5-mediated m 6 A demethylation.Finally, our data demonstrated that ALKBH5 promoted SKCM via mediating ABCA1 downregulation by reducing ABCA1 mRNA stability in an m 6 A-dependent manner.Conclusion: Our findings exhibited the functional value of the key demethylase ALKBH5 mediated m 6 A modification in the progression of SKCM, suggesting the ALKBH5-m 6 A-ABCA1 axis as a potential therapeutic target in SKCM.

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