Review Article

m⁶A modification in cancer regulation: molecular circuits and regulatory networks

Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, PR China

^* Corresponding author: xiashutj@hust.edu.cn

Received: 29 April 2025
Accepted: 5 July 2025

Abstract

The N6-methyladenosine (m⁶A) modification is a significant research direction in the field of epitranscriptomics, and its multifaceted functions in tumor regulation have garnered increasing attention. Through the actions of three core enzyme groups, writers, erasers, and readers, m⁶A modification dynamically regulates RNA stability, translation efficiency, and localization, thereby influencing key biological processes in tumor cells, such as proliferation, metastasis, and drug resistance. This review outlines the m⁶A modification’s regulatory roles in tumor autophagy and apoptosis, metabolic reprogramming, and dynamic alterations within the tumor microenvironment. Specifically, it elaborates on how m⁶A orchestrates microenvironmental remodeling to promote tumor progression through mechanisms including autophagy signaling transduction, apoptotic gene regulation, metabolic gene modulation, as well as functional reprogramming of immune cells and endothelial cells. Although significant progress has been made in m⁶A-related tumor research, challenges remain, including its dynamic and reversible regulatory mechanisms, heterogeneity-driven functional differences, and clinical translation applications. Future studies should further explore the specific regulatory mechanisms of m⁶A modification, develop targeted therapeutic strategies, and integrate multi-omics and artificial intelligence technologies to construct dynamic regulatory network models. These efforts will facilitate the translation of basic research findings into clinical applications, providing novel insights and strategies for tumor diagnosis and treatment.