5-methylcytosine (m5C) modification has emerged as a novel epigenetic modification of ribonucleic acids (RNAs), encompassing messenger RNAs (mRNAs) and non- coding RNAs, in recent years. This reversible modification, which is regulated by m5C regulators consisting of methyltransferases, demethyltransferases, and RNA-binding proteins, modulates all aspects of RNA metabolism and gene expression. Gastrointestinal (GI) cancers are prevalent malignancies with a high mortality rate globally. Accumulating evidence has indicated the significant role of m5C RNA modification in the tumorigenesis and progression of GI cancers. In this review, we provide a comprehensive overview of the functions and underlying molecular mechanisms of m5C RNA modification in RNA metabolism for the regulation of tumor biology, including cell proliferation, apoptosis, invasion/metastasis, chemoresistance, and other biological functions. Furthermore, we summarize the specific role of m5C modification in GI cancers and propose some insights regarding its application as a tumor biomarker and therapeutic target, aiming to offer a new perspective for m5C modification in GI cancer diagnosis and treatment in the future.
Xu et al. (2026) studied this question.