Role and mechanisms of m6A demethylases in digestive system tumors

Digestive system tumors are common malignancies in humans, often accompanied by high mortality and poor prognosis. Therefore, intensive research on the pathogenesis of digestive system tumors is imperative. N6-methyladenosine (m6A) is the most common RNA modification in eukaryotes and exerts regulatory effects on RNA expression and metabolism, including splicing, translation, stability, decay, and transport. m6A demethylases belong to the AlkB family of dioxygenases that can catalyze m6A demethylation. Accumulating evidence in recent years has shown that abnormal m6A levels caused by m6A demethylases play crucial roles in different aspects of human cancer development. In this review, we comprehensively summarize the recent findings on the functions and underlying molecular mechanisms of m6A demethylases in cell proliferation, apoptosis, migration, invasion, metastasis, angiogenesis, resistance to chemo- and radiotherapy, and the tumor immune microenvironment (TIME) of digestive system tumors. Furthermore, we discuss the therapeutic potential of targeting these m6A demethylases for treatment.