The role, regulatory mechanisms, and therapeutic implications of FTO in gastrointestinal cancer

N6-methyladenosine (m6A) is the most common post-transcriptional modification in mRNA, playing a crucial role in cancer development by modulating RNA stability, translation, and nuclear export. As the first discovered m6A demethylase, FTO catalyzes m6A demethylation in a Fe 2+ /α-KG-dependent manner, functioning as either an oncogene or a tumor suppressor to mediate cancer progression via reducing m6A levels and thereby modulating RNA metabolism. Numerous studies have elucidated the mechanisms by which upstream regulators affect FTO expression, as well as the post-translational modifications that impact its protein stability, translocation, and degradation. Moreover, inhibitors targeting FTO demonstrate significant therapeutic potential. In this review, we summarize recent research on the role and regulatory manner of FTO in gastrointestinal cancer and discuss its potential clinical application in cancer therapy.