The roles and implications of RNA m6A modification in cancer

• Published in: Nature reviews. Clinical oncology Vol. 20; no. 8; pp. 507 - 526
• Main Authors: Deng, Xiaolan, Qing, Ying, Horne, David, Huang, Huilin, Chen, Jianjun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.08.2023
• Subjects: Biomarkers; Cancer; Cancer therapies; Cell self-renewal; Metastases; Molecular modelling; mRNA; N6-methyladenosine; Phenotypes; RNA modification; Tumor microenvironment; Tumors
• ISSN: 1759-4774; 1759-4782
• DOI: 10.1038/s41571-023-00774-x

N6-Methyladenosine (m6A), the most prevalent internal modification in eukaryotic mRNA, has been extensively and increasingly studied over the past decade. Dysregulation of RNA m6A modification and its associated machinery, including writers, erasers and readers, is frequently observed in various cancer types, and the dysregulation profiles might serve as diagnostic, prognostic and/or predictive biomarkers. Dysregulated m6A modifiers have been shown to function as oncoproteins or tumour suppressors with essential roles in cancer initiation, progression, metastasis, metabolism, therapy resistance and immune evasion as well as in cancer stem cell self-renewal and the tumour microenvironment, highlighting the therapeutic potential of targeting the dysregulated m6A machinery for cancer treatment. In this Review, we discuss the mechanisms by which m6A modifiers determine the fate of target RNAs and thereby influence protein expression, molecular pathways and cell phenotypes. We also describe the state-of-the-art methodologies for mapping global m6A epitranscriptomes in cancer. We further summarize discoveries regarding the dysregulation of m6A modifiers and modifications in cancer, their pathological roles, and the underlying molecular mechanisms. Finally, we discuss m6A-related prognostic and predictive molecular biomarkers in cancer as well as the development of small-molecule inhibitors targeting oncogenic m6A modifiers and their activity in preclinical models.Dysregulation of N6-methyladenosine (m6A), the most prevalent internal modification in eukaryotic mRNA, is common in various cancer types. The authors of this Review provide an overview of the mechanisms of m6A-dependent RNA regulation, summarize current knowledge of their pathological effects and potential utility as biomarkers in cancer, and describe ongoing efforts to develop small-molecule inhibitors of oncogenic m6A modifiers.