Role of m6A RNA Methylation in T Cell Biology and Immunotherapy

Epitranscriptomic regulation of mRNAs and noncoding RNAs by m6A in hepatocellular carcinoma.

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.

The role of m6A RNA methylation in skeletal muscle pathophysiology and its targeted therapeutic prospects.

m6A RNA methylation in breast cancer: from epitranscriptomic regulation to therapeutic targeting.

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.

RNA modifications in cancer: regulators of tumor evolution and therapeutic response.

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.

RNA epitranscriptomic regulation of tumor immune evasion: mechanisms, context-dependent roles, and therapeutic implications

Tumor immune evasion is a fundamental hallmark of cancer progression and a major barrier to effective immunotherapy. RNA epitranscriptomic modifications have emerged as a critical layer of post-transcriptional regulation that links RNA fate control with tumor immune remodeling. These reversible modifications, including m6A, m5C, ac4C, m¹A, m7G, pseudouridine, m6Am, Nm, and A-to-I RNA editing, are dynamically regulated by writers, erasers, and readers. By modulating RNA stability, splicing, nuclear export, translation efficiency, degradation, and innate immune recognition, RNA modifications reshape multiple immune-related processes in cancer. Mechanistically, they regulate tumor immune visibility by influencing antigen processing, MHC-I expression, interferon signaling, and dendritic cell-mediated cross-presentation. They also control immune checkpoint expression, particularly the PD-1/PD-L1 axis, inflammatory signaling pathways, immune-cell recruitment and exhaustion, and metabolic immunosuppression within the tumor immune microenvironment. Importantly, the functions of RNA modification regulators are highly context dependent. The same regulator may either promote immune escape or enhance antitumor immunity depending on cancer type, cellular source, target transcript, reader protein, and microenvironmental state. From a clinical perspective, RNA modification-based molecular subtypes, prognostic signatures, and risk-score models show potential for predicting patient prognosis, immune infiltration, and response to immune checkpoint blockade. In parallel, targeting RNA modification regulators, alone or in combination with immunotherapy, radiotherapy, chemotherapy, or targeted therapy, represents an emerging therapeutic strategy. However, clinical translation remains limited by insufficient specificity, tumor heterogeneity, complex crosstalk among RNA modifications, potential toxicity, and delivery barriers. Future studies integrating RNA modification mapping with single-cell, spatial, and multi-omics technologies will be essential to define cell-type-specific regulatory networks and develop precise RNA epitranscriptomic biomarkers and therapies for cancer immunotherapy.

RNA modifications as determinants of cancer cell death: from epitranscriptomic mechanisms to therapeutic targeting

It is argued that while epitranscriptomics represents a compelling regulatory axis in cancer cell death, advancing the field will require integrative, high-resolution, and functionally precise approaches to move beyond correlative frameworks toward mechanistic and clinically actionable insights.