Epigenetic modification of m⁶A regulator proteins in cancer

Divergent N₆-methyladenosine (m⁶A) modifications are dynamic and reversible posttranscriptional RNA modifications that are mediated by m⁶A regulators or m⁶A RNA methylation regulators, i.e., methyltransferases ("writers"), demethylases ("erasers"), and m⁶A-binding proteins ("readers"). Aberrant m⁶A modifications are associated with cancer occurrence, development, progression, and prognosis. Numerous studies have established that aberrant m⁶A regulators function as either tumor suppressors or oncogenes in multiple tumor types. However, the functions and mechanisms of m⁶A regulators in cancer remain largely elusive and should be explored. Emerging studies suggest that m⁶A 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 m⁶A regulators in cancer. The roles and mechanisms for epigenetic modification of m⁶A regulators in cancer genesis are segregated. The review will improve the understanding of the epigenetic regulatory mechanisms of m⁶A regulators.