N6-methyladenosine demethylase FTO promotes growth and metastasis of gastric cancer via m 6 A modification of caveolin-1 and metabolic regulation of mitochondrial dynamics.

Gastric cancer (GC) is the fifth most common tumor and the third most deadly cancer worldwide. N6-methyladenosine (m 6 A) modification has been reported to play a regulatory role in human cancers. However, the exact role of m 6 A in GC remains largely unknown, and the dysregulation of m 6 A on mitochondrial metabolism has never been studied. In the present study, we demonstrated that FTO, a key demethylase for RNA m 6 A 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 m 6 A demethylation modification and could be used as a new strategy for more careful surveillance and aggressive therapeutic intervention.