Epitranscriptomics in Breast Cancer: The Unveiled Role of RNA Modifications

Epitranscriptomics, the study of dynamic chemical modifications on RNA molecules, has emerged as a pivotal layer of gene expression regulation with profound implications for cancer biology. This review centers on three well-characterized RNA modifications, N6-methyladenosine (m6A), pseudouridine (Ψ), and 5-methylcytosine (m5C), and highlights their diverse roles in the pathogenesis of breast cancer. These modifications modulate critical post-transcriptional processes such as RNA splicing, stability, translation, and degradation, thereby influencing tumor initiation, progression, metastasis, therapy resistance, and interactions within the tumor microenvironment. Also the study briefly explores emerging modifications, including Adenosine-to-Inosine (A-to-I) editing and N1-methyladenosine (m1A), which add further complexity to the epitranscriptomic landscape. Advances in high-throughput sequencing, bioinformatics, and single-cell technologies have significantly deepened understanding of the context-dependent and reversible nature of these modifications. Importantly, RNA modification signatures show promise as non-invasive biomarkers and therapeutic targets. However, translating these insights into clinical applications remains challenging due to issues related to delivery mechanisms, specificity, and regulatory hurdles. This review provides a comprehensive synthesis of current knowledge, highlights key controversies and technological limitations, and discusses future directions for leveraging epitranscriptomics in the early detection and personalized treatment of breast cancer.