Mechanism and therapeutic prospects of ferroptosis regulation through m6A in cancer
TL;DR
This review systematically elucidates the multidimensional regulatory mechanisms of m6A on ferroptosis regulatory factors, covering post-transcriptional modifications of the System Xc−/GSH/GPX4 antioxidant axis, iron metabolism-related proteins, and key enzymes of lipid peroxidation.
Abstract
N6-methyladenosine (m6A), as the most abundant epitranscriptomic modification in eukaryotes, profoundly influences the metabolic fate of RNA. Meanwhile, ferroptosis, a regulated cell death modality driven by iron-dependent lipid peroxidation, has become a key component in tumor metabolic reprogramming. Increasing evidence suggests a deep interaction between m6A modification and ferroptosis, which plays a critical role in tumor occurrence and development, and treatment response. This review systematically elucidates the multidimensional regulatory mechanisms of m6A on ferroptosis regulatory factors, covering post-transcriptional modifications of the System Xc−/GSH/GPX4 antioxidant axis, iron metabolism-related proteins, and key enzymes of lipid peroxidation. It analyzes the dual role of the m6A-ferroptosis axis in tumor suppression and promotion, and then explores the function of this regulatory network in reshaping the tumor immune microenvironment and mediating treatment resistance. Finally, it looks forward to the translational potential of the m6A-ferroptosis interactive network as a novel biomarker and combination therapy target. Future research should integrate multi-omics and cutting-edge technologies to deeply analyze the spatiotemporal dynamic mechanism of this regulatory network in the occurrence and development of tumors, providing theoretical basis and new research directions for precise intervention in this interdisciplinary field.