Regulation of m⁶A Methylome in Cancer: Mechanisms, Implications, and Therapeutic Strategies

Reversible <i>N</i>⁶-adenosine methylation of mRNA, referred to as m⁶A modification, has emerged as an important regulator of post-transcriptional RNA processing. Numerous studies have highlighted its crucial role in the pathogenesis of diverse diseases, particularly cancer. Post-translational modifications of m⁶A-related proteins play a fundamental role in regulating the m⁶A methylome, thereby influencing the fate of m⁶A-methylated RNA. A comprehensive understanding of the mechanisms that regulate m⁶A-related proteins and the factors contributing to the specificity of m⁶A deposition has the potential to unveil novel therapeutic strategies for cancer treatment. This review provides an in-depth overview of our current knowledge of post-translational modifications of m⁶A-related proteins, associated signaling pathways, and the mechanisms that drive the specificity of m⁶A modifications. Additionally, we explored the role of m⁶A-dependent mechanisms in the progression of various human cancers. Together, this review summarizes the mechanisms underlying the regulation of the m⁶A methylome to provide insight into its potential as a novel therapeutic strategy for the treatment of cancer.