Refining the role of N6-methyladenosine in cancer

Abstract

N⁶-methyladenosine (m⁶A) is the most abundant internal modification of eukaryotic mRNAs. m⁶A affects the fate of its targets in all aspects of the mRNA life cycle and has important roles in various physiological and pathophysiological processes. Aberrant m⁶A patterns have been observed in numerous cancers and appear closely linked to oncogenic phenotypes. However, most studies relied on antibody-dependent modification detection, which is known to suffer from important limitations. Novel, antibody-independent, quantitative approaches will be critical to investigate changes in the m⁶A landscape of cancers. Furthermore, pharmaceutical targeting of the m⁶A writer Methyltransferase-like 3 (METTL3) has demonstrated the potential to modulate cancer cell phenotypes. However, the enzyme also appears to be essential for the viability of healthy cells. Further refinement of therapeutic strategies is therefore needed to fully realize the potential of m⁶A-related cancer therapies.