N6-methyladenosine demethylase FTO promotes growth and metastasis of gastric cancer via m6A modification of caveolin-1 and metabolic regulation of mitochondrial dynamics

Abstract

Abstract Gastric cancer (GC) is the fifth most common tumor and the third most deadly cancer worldwide. N6-methyladenosine (m6A) modification has been reported to play a regulatory role in human cancers. However, the exact role of m6A in GC remains largely unknown, and the dysregulation of m6A on mitochondrial metabolism has never been studied. In the present study, we demonstrated that FTO, a key demethylase for RNA m6A modification, was up-regulated in GC tissues, especially in tissues with liver metastasis. Functionally, FTO acted as a promoter for the proliferation and metastasis in GC. Moreover, FTO enhanced the degradation of caveolin-1 mRNA via its demethylation, which regulated the mitochondrial fission/fusion and metabolism. Collectively, our current findings provided some valuable insights into FTO-mediated m6A demethylation modification and could be used as a new strategy for more careful surveillance and aggressive therapeutic intervention.