Jul 2026· Frontiers in Cell and Developmental Biology· Vol 14· 0 citations· 455 references
Medicine
TL;DR
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, and comprehensively dissects the bidirectional crosstalk among the three core functional modules within this network.
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.
The molecular mechanisms by which m6A regulates both coding and noncoding RNAs in HCC are summarized, the functional roles of key m6A regulators in hepatocarcinogenesis are highlighted, and the therapeutic potential of targeting the m6A machinery in HCC is discussed.
Xinning Luo, Cuiying Qin, Yi Feng et al.· Discover Oncology· 0 citations
RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), and adenosine-to-inosine (A-to-I) editing, constitute a dynamic epitranscriptomic network that profoundly regulates RNA metabolism and gene expression. Their dysregulation is increasingly recognized as a hallmark of cancer. This review critically synthesizes the multifaceted roles of RNA modifications to bridge the gap between descriptive epitranscriptomic mapping and functional tumor biology. We systematically evaluate how writers, readers, and erasers dictate transcript stability and translation efficiency, driving tissue-specific tumor evolution across diverse malignancies. Crucially, we explore the intersection of RNA modifications and the tumor immune microenvironment, detailing their mechanisms in orchestrating immune evasion, altering antigen presentation, and regulating immune checkpoints. Furthermore, we examine how epitranscriptomic reprogramming dictates cellular responses to chemotherapy, radiotherapy, targeted treatments, and immunotherapy. By comprehensively analyzing these mechanisms, this review aims to facilitate the translation of epitranscriptomic findings into clinical applications, laying a theoretical foundation for targeted anti-tumor strategies.
N6-methyladenosine (m6A) modification is the most common epigenetic alteration in eukaryotic mRNA, significantly impacting metabolic reprogramming and the tumor microenvironment (TME) of colorectal cancer (CRC) by dynamically regulating RNA metabolic processes. Recent studies indicate that m6A modification interacts with CRC metabolic reprogramming, fostering an immunosuppressive TME. Specifically, m6A modification promotes CRC progression by regulating glucose, lipid, and amino acid metabolism while inhibiting the activity of antitumor immune cells (such as T cells, natural killer cells, and macrophages) and activating tumor immunosuppressive cells (including tumor-associated macrophages, myeloid-derived suppressor cells, regulatory T cells, tumor-associated neutrophils, and cancer-associated fibroblasts). This article systematically reviews the molecular mechanisms through which m6A modification drives the malignant progression of CRC via metabolic regulation, elucidates the metabolic network involving m6A modification and its role in shaping TME, and discusses the clinical potential of targeting m6A modification and/or metabolic pathways, offering novel research avenues for CRC treatment.
Liang Zhao, Zhi-tao Yin, Chen-Chun Ji et al.· Frontiers in Immunology· 0 citations
N6-methyladenosine (m6A) RNA methylation is the most prevalent internal modification in eukaryotic mRNA and precisely regulates gene expression by regulating the RNA life cycle. Lactate, a central glycolytic metabolite, can transduce cellular metabolic states into epigenetic signals through protein lactylation, an emerging post-translational modification. Because both modifications are highly responsive to cellular metabolic status, they have emerged as important regulators of the metabolic-epigenetic interface. Increasing evidence supports a bidirectional regulatory crosstalk between m6A modification and protein lactylation. Lactate accumulation can modulate the expression and activity of m6A-related regulatory enzymes through histone and non-histone lactylation; conversely, m6A modification can reshape glycolysis and lactate metabolism, thereby altering lactate availability and protein lactylation. This reciprocal regulation has been implicated in a broad spectrum of diseases, including cancer, metabolic disorders, cardiovascular diseases, and immune-inflammatory conditions. In this review, the molecular mechanisms of m6A modification and protein lactylation are systematically summarized, with particular emphasis on their modes of interaction and pathological relevance. Current limitations and future perspectives are also discussed, providing a conceptual framework for elucidating disease mechanisms and developing therapeutic strategies targeting this regulatory network.
Y. Gong, Yu Liu· Journal of Translational Med...· 0 citations
Breast cancer remains a leading cause of cancer-related mortality worldwide, largely due to its molecular heterogeneity and therapeutic resistance. N6-methyladenosine (m6A) RNA modification has recently emerged as a critical epitranscriptomic regulator involved in diverse aspects of RNA metabolism, including stability, splicing, translation, and degradation. Accumulating evidence suggests that dysregulation of m6A modification is associated with breast cancer progression, metastasis, and treatment resistance. In this review, we systematically summarize the functional roles of m6A regulators, including writers, erasers, and readers, in breast cancer biology. We further discuss the involvement of m6A modification in key oncogenic signaling pathways, metabolic reprogramming, and tumor immune microenvironment remodeling. Importantly, we highlight the emerging clinical potential of m6A regulators as diagnostic and prognostic biomarkers, as well as therapeutic targets for overcoming drug resistance. Finally, we outline current challenges and future perspectives, emphasizing the need for integrating multi-omics approaches and developing m6A-targeted therapies to advance precision oncology in breast cancer.
Zilong Chen, Chi-Cheng Zhou, Zhuorun Song et al.· Cancer Treatment and Researc...· 0 citations
This review focuses on the interplay between immunity and epitranscriptomics and explores the direct and indirect effects of m6A modification on T cells and highlights the pivotal role of m6A regulation in T cell biology and its potential to optimize next-generation immunotherapies.
Yumna A. Butt, Nordin D. Zandhuis, I. Foskolou· Immuno· 0 citations