ALKBH5-mediated mA demethylation of FOXM1 mRNA promotes progression of uveal melanoma.

In this study, we found that ALKBH5, a key component of the -methyladenosine (mA) methyltransferase complex, was significantly elevated in uveal melanoma (UM) cell lines and that ALKBH5 downregulation inhibited tumor growth . High ALKBH5 expression predicted worse outcome in patients with UM. EP300-induced H3K27 acetylation activation increased ALKBH5 expression. Downregulation of ALKBH5 inhibited UM cell proliferation, migration, and invasion and increased apoptosis . Besides, ALKBH5 may promote UM metastasis by inducing epithelial-to-mesenchymal transition (EMT) via demethylation of mRNA, which increases its expression and stability. In sum, our study indicates that AKLBH5-induced mA demethylation of mRNA promotes UM progression. Therefore, AKLBH5 is a potential prognostic biomarker and therapeutic target in UM.