MiR-155 regulates m⁶A level and cell progression by targeting FTO in clear cell renal cell carcinoma

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.