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.
Abstract
N6-methyladenosine (m6A) is a major epitranscriptomic modification of RNA that plays a crucial role in regulating RNA metabolism and function, thereby participating in diverse biological processes such as cellular homeostasis and stress responses. The dynamic regulation of m6A is orchestrated by three classes of proteins: methyltransferases that install the modification, demethylases that remove it, and m6A-binding proteins that recognize modified transcripts and mediate downstream effects. Accumulating evidence has shown that dysregulation of m6A is critically involved in the initiation and progression of various malignancies. Hepatocellular carcinoma (HCC), a primary liver malignancy with high mortality and poor prognosis, has also been closely linked to m6A-mediated RNA regulation. In this review, we summarize the molecular mechanisms by which m6A regulates both coding and noncoding RNAs in HCC, highlight the functional roles of key m6A regulators in hepatocarcinogenesis, and discuss the therapeutic potential of targeting the m6A machinery in HCC.
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
A model in which mRNA modifications act combinatorially to regulate mRNA homeostasis in plants is supported, including advances in profiling technologies, single-base resolution methods, and nanopore direct RNA sequencing.
Thi Tuyet Suong Ha, S. Park, Dong-Hoon Jeong· Journal of Plant Biology· 0 citations
As a key N6-methyladenosine (m6A)-binding protein, YT521-B Homology (YTH) Domain-Containing Protein 2 (YTHDC2) plays a central role in the epitranscriptomic regulatory network. This protein specifically recognizes and binds to m6A modification sites on RNA molecules through its highly conserved YTH domain. This recognition exhibits high selectivity and affinity, thereby enabling precise control over the fate of target RNAs. At the molecular level, YTHDC2 is widely involved in various stages of the RNA life cycle, including core biological processes such as RNA splicing and processing, nuclear–cytoplasmic transport, translational efficiency regulation, and RNA decay. In recent years, accumulating evidence indicates that YTHDC2 participates in a variety of pathophysiological processes in an m6A-dependent manner. However, the robustness of evidence regarding YTHDC2 is heterogeneous across disease contexts. While certain pathologies are supported by rigorous mechanistic validation, others rely primarily on expression correlations or bioinformatic analyses. This review systematically synthesizes current knowledge regarding the multifaceted roles of YTHDC2 in disease progression, prognosis, and therapy, offering a comprehensive framework to guide future investigations.
Yan-Ying Hu, Qi Zhou, Ning Xu et al.· Cells· 0 citations
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.
A. Mukherjee, Ankit Kumar Bharti, D. Mathew et al.· Functional & Integrative Gen...· 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.
This review explores how isomiR generation, miRNA strand selection, arm switching, and epitranscriptomic regulation expand the functional diversity of miRNAs in gynecologic cancers.
Y. Pérez-Navarro, C. López-Camarillo, L. C. Flores-García et al.· International Journal of Mol...· 0 citations
