This comprehensive review by Prof. Zili Zhang, Prof. Mei Guo, and their collaborators at Nanjing University of Chinese Medicine systematically outlines the dual role of m⁶A modification in promoting and suppressing tumours across various cancer types.

The authors describe how m⁶A methylation dynamically regulates key oncogenic pathways, cancer stemness, immune evasion, and metabolic reprogramming within the tumour microenvironment.

The research is published in the journal Molecular Biomedicine.

The review emphasises that m⁶A influences nearly all stages of RNA metabolism—including splicing, stability, translation, and decay—thereby affecting the expression of critical oncogenes and tumour suppressors.

Dysregulation of m⁶A, driven by abnormal expression of writers (e.g., METTL3, METTL14), erasers (e.g., FTO, ALKBH5), and readers (e.g., the YTHDF family, IGF2BPs), can promote cancer hallmarks such as uncontrolled proliferation, resistance to cell death, metastasis, and angiogenesis.

Importantly, the review highlights the clinical relevance of m⁶A and explores:

1. the diagnostic and prognostic potential of m⁶A regulators in cancers such as colorectal cancer, hepatocellular carcinoma, and acute myeloid leukaemia;
2. mechanisms of therapy resistance mediated by m⁶A, including chemoresistance and radioresistance;
3. emerging therapeutic approaches, including small-molecule inhibitors (e.g., STM2457 for METTL3, FB23-2 for FTO), CRISPR-dCas13–based m⁶A editing, and combination strategies with immunotherapy.

The authors also discuss the potential of m⁶A-based personalised medicine, where patient-specific m⁶A profiles could guide treatment selection and monitoring via liquid biopsies.

Collectively, this work positions m⁶A modification as a central epigenetic mechanism in cancer and a promising frontier for the development of next-generation RNA-targeted therapies.

Source: Sichuan International Medical Exchange and Promotion Association