Abstract
Although FTO, as an eraser of N6-methyladenosine (m6A), plays context-dependent tumor-suppressive and oncogenic roles in various cancer type, underlying molecular events of its aberrant expression in cancers is complex and still poorly understood. Here we show that miR-155 directly targets FTO to negatively regulate its expression and increased m6A level in ccRCC. Combining bioinformatics analysis and luciferase reporter assays, we identified that miR-155 directly bound to the 3'UTR of FTO mRNA and reduced FTO protein levels in ccRCC cells. Moreover, cell function assays, xenografts assays and m6A dot blot assays revealed that overexpression of miR-155 enhanced tumor cell proliferation and global mRNA m6A level, while decreasing apoptosis in a FTO-dependent manner. Collectively, our data demonstrates the functional importance of miR-155 in regulating FTO expression and global mRNA m6A level, and provides profound insights into ccRCC tumorigenesis.