Emerging Regulatory Mechanisms of N⁶-Methyladenosine Modification in Cancer Metastasis

Cancer metastasis is the major cause of cancer-related deaths and accounts for poor therapeutic outcomes. A metastatic cascade is a series of complicated biological processes. N⁶-methyladenosine (m⁶A) is the most abundant and conserved epitranscriptomic modification in eukaryotic cells, which has great impacts on RNA production and metabolism, including RNA splicing, processing, degradation and translation. Accumulating evidence demonstrates that m⁶A plays a critical role in regulating cancer metastasis. However, there is a lack of studies that review the recent advances of m⁶A in cancer metastasis. Here, we systematically retrieved the functions and mechanisms of how the m⁶A axis regulates metastasis, and especially summarized the organ-specific liver, lung and brain metastasis mediated by m⁶A in various cancers. Moreover, we discussed the potential application of m⁶A modification in cancer diagnosis and therapy, as well as the present limitations and future perspectives of m⁶A in cancer metastasis. This review provides a comprehensive knowledge on the m⁶A-mediated regulation of gene expression, which is helpful to extensively understand the complexity of cancer metastasis from a new epitranscriptomic point of view and shed light on the developing novel strategies to anti-metastasis based on m⁶A alteration.