Epigenetic modification of m(6)A regulator proteins in cancer

Divergent N(6)-methyladenosine (m(6)A) modifications are dynamic and reversible posttranscriptional RNA modifications that are mediated by m(6)A regulators or m(6)A RNA methylation regulators, i.e., methyltransferases (“writers”), demethylases (“erasers”), and m(6)A-binding proteins (“readers”). Aberrant m(6)A modifications are associated with cancer occurrence, development, progression, and prognosis. Numerous studies have established that aberrant m(6)A regulators function as either tumor suppressors or oncogenes in multiple tumor types. However, the functions and mechanisms of m(6)A regulators in cancer remain largely elusive and should be explored. Emerging studies suggest that m(6)A regulators can be modulated by epigenetic modifications, namely, ubiquitination, SUMOylation, acetylation, methylation, phosphorylation, O-GlcNAcylation, ISGylation, and lactylation or via noncoding RNA action, in cancer. This review summarizes the current roles of m(6)A regulators in cancer. The roles and mechanisms for epigenetic modification of m(6)A regulators in cancer genesis are segregated. The review will improve the understanding of the epigenetic regulatory mechanisms of m(6)A regulators.