Abstract
RNA modification, a prominent epigenetic mechanism, has been implicated in regulating RNA function, stability, processing, and interactions, including pseudouridylation, acetylation, and methylation. Recent evidence highlights that 5-methylcytosine (m5C) influences key cellular processes such as proliferation, differentiation, apoptosis, and stress responses by modulating RNA stability, translation, transcription, nuclear export, and cleavage. This review consolidates current insights into the role and mechanisms of m5C methylation across various tumor types, underscoring its pivotal involvement in post-transcriptional regulation and its profound effects on gene expression, cellular dynamics, and tumor biology. The mechanisms through which m5C methylation impacts tumor progression, including modulation of glucose and iron metabolism, as well as resistance to therapeutic agents, are also discussed. Finally, the review identifies critical future research avenues, focusing on elucidating the underlying mechanisms, developing targeted therapies, and advancing personalized medicine approaches to leverage m5C methylation in cancer treatment.