m6A RNA modification: a central epitranscriptomic switch orchestrating oncogenic signaling and glycolytic reprogramming in cancer

Abstract

N6-methyladenosine (m6A) is the most widespread, abundant, and conserved post-transcriptional modification in eukaryotic RNA, and it participates in the regulation of various biological processes, especially playing a crucial role in tumorigenesis and progression. During tumor progression, abnormal expression of m6A regulatory proteins often leads to dysregulation of m6A modification levels, thereby affecting tumor pathophysiology. Recent studies have shown that in various tumor types, m6A modifications on target mRNAs and non-coding RNA transcripts can regulate the activity of various oncogenic signaling pathways; moreover, m6A modifications can also regulate the tumor glycolysis process through multiple molecular mechanisms, thereby affecting the proliferation, invasion, and metastasis of tumor cells and other biological behaviors. Most existing reviews focus only on the unidirectional regulatory relationships among m6A modification, oncogenic signaling, and glycolysis, while overlooking the crosstalk among the three. To address this gap, this review systematically summarizes the regulatory effects of m6A modifications on key glycolytic enzymes and various cancer signaling pathways, examines in depth the molecular mechanisms by which the three cooperatively participate in tumorigenesis and progression, comprehensively dissects the bidirectional crosstalk among the three core functional modules within this network, and further proposes a self-stabilizing “m6A–signaling–glycolysis closed-loop regulatory network,” and provides future research directions for this field. It offers theoretical references for related basic research and clinical diagnosis and treatment.