RNA epigenetic modifications as dynamic biomarkers in cancer: from mechanisms to clinical translation.

RNA modifications are crucial for post-transcriptional gene regulation. Research on RNA modifications has become a novel frontier of epitranscriptomics. Up to now, over 170 kinds of modifications have been identified on mRNA and diverse non-coding RNA. Three classes of proteins (writers, erasers, and readers) regulate the addition, removal, and identification of epigenetic marks, thus affecting RNA biological functions. Increasing evidence identifies the dysregulation of RNA modifications in different cancer types and the therapeutic potential of targeting RNA-modifying enzymes. The ability of RNA modifications to improve mRNA stability and translation efficacy and decrease immunogenicity has been exploited for the clinical use of mRNA cancer vaccines. This review aims to shed light on several vital cap, tail, and internal modifications of RNA with a focus on the connection between RNA epigenetic pathways and cancer pathogenesis. We further explore the clinical potential of RNA modifications as dynamic biomarkers for cancer diagnosis, prognosis, and therapeutic response prediction, addressing both technological challenges and translational opportunities. Finally, we analyze the limitations of current studies and discuss the research focus in the future.