The novel roles of RNA 5-methylcytosine modification in gastrointestinal tract cancers

Gastrointestinal tract cancers, including esophageal carcinoma (ESCA), gastric cancer (GC), and colorectal carcinoma (CRC), are among the most common malignant tumors with high morbidity and mortality rates, posing an increasingly significant burden on social healthcare systems. Recent evidence revealing the association between RNA modifications (collectively termed epitranscriptomics) and the tumorigenesis of gastrointestinal tract cancers has provided new insights into their pathogenesis. Among these modifications, 5-methylcytosine (m5C) is one of the most prevalent. In this narrative review, we discuss the regulators and functions of RNA m5C modification, summarize the recent studies on the roles of m5C modification in gastrointestinal tract cancer cells, briefly explore the association between RNA m5C modification and the tumor microenvironment (TME), and provide insights into its potential clinical applications as well as the remaining challenges in utilizing m5C modification for the management of gastrointestinal tract cancers. This review is based on comprehensive literature searches conducted primarily in PubMed, with no restrictions on publication date. Relevant articles were selected according to their relevance to the scope and objectives of this review. Although increasing evidence has elucidated the molecular mechanisms by which m5C RNA modification regulates the development and progression of gastrointestinal tract cancers, clinical evidence supporting its application in early screening or as a therapeutic target remains limited. Current findings are mainly derived from experimental studies and exploratory clinical studies, suggesting the gap between mechanistic insights and clinical translation.