Epigenetic modification of m ⁶A regulator proteins in cancer

Abstract

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