Recent advances in m6A RNA modification in hepatocellular carcinoma: from mechanisms to therapeutic potential

Hepatocellular carcinoma (HCC) remains a major global health burden due to its high incidence and mortality, underscoring the urgent need to elucidate the molecular mechanisms of HCC and to improve diagnosis and therapeutic approaches. As the most prevalent form of mRNA modification, N6-methyladenosine (m6A) plays a central role in regulating diverse cellular processes in both physiological and pathological conditions, particularly in cancer initiation, development, and progression. This comprehensive review systematically outlines the biological function of three primary classes of m6A regulator proteins, “writers”, “erasers”, and “readers”. It further examines the dysregulated expression patterns of m6A regulators in HCC, analyzes their clinical associations with tumor grade, clinical stage, and survival outcomes, and evaluates their functional contributions to key oncogenic processes, including cell proliferation, apoptosis, and metastasis. Moreover, this review highlights the critical involvement of m6A RNA modification in orchestrating major molecular mechanisms in HCC, offering an in-depth analysis of its regulatory effects on glycolysis, lipid metabolism, ferroptosis, cancer stemness, tumor immunity, cell cycle progression, and resistance to therapy. Finally, the review synthesizes current progress in emerging therapeutic strategies that target the m6A RNA modification for the treatment of HCC. In conclusion, this review presents a systematic summary of recent advances in m6A RNA modification in HCC, delivering valuable insights for future basic and translational studies. Ongoing research into m6A-mediated regulatory mechanisms hold promise for transforming diagnostic paradigms and enabling the development of innovative therapeutic strategies for patients with HCC.