m6A RNA Methylation and Cancer Progression: Pathogenesis, Implications, and Therapeutic Potential

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DOI: 10.21522/TIJPH.2013.SE.24.05.Art015

Authors : Geetha Shanmugam, Abin Mahmood Nizar

Abstract:

N6-methyladenosine (m6A) is a prominent internal modification of eukaryotic messenger RNA (mRNA) and has garnered significant attention due to its regulatory role in various biological processes, particularly in cancer. As a dynamic and reversible modification, m6A is orchestrated by three key players: Writers, primarily methyltransferases like METTL3 and METTL14, add m6A marks to mRNA, influencing processes such as RNA stability and translation. Erasers, such as FTO and ALKBH5, remove these marks, enabling the fine-tuning of mRNA functions. Readers, including YTH domain-containing proteins (e.g., YTHDF1, YTHDF2), recognize and bind to m6A-modified mRNA, directing its fate in terms of degradation, translation efficiency, or cellular localization. In cancer, m6A modifications have been implicated in promoting tumor progression by affecting gene expression at the post-transcriptional level. The dysregulation of m6A machinery can lead to aberrant expression of oncogenes or tumor suppressors, thereby driving oncogenesis Furthermore, m6A modifications play a crucial role in modulating the tumor microenvironment (TME) and immune evasion. By altering the expression of cytokines, chemokines, and immune checkpoint molecules, m6A can influence immune cell infiltration and activation, impacting the anti-tumor immune response. This modulation of the TME not only aids in tumor progression but also presents challenges and opportunities for cancer immunotherapy. Given its profound impact on cancer biology, targeting the m6A machinery holds therapeutic potential. Small molecules or inhibitors designed to modulate m6A writers, erasers, or readers could offer new avenues for cancer treatment, making m6A a promising target in the fight against cancer.

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