Circular RNAs in colorectal cancer: Emerging insights and future perspectives

Circular RNAs (circRNAs) are a distinct class of long non-coding RNAs characterized by their covalently closed-loop structure, which confers high stability. Once dismissed as nonfunctional ’junk RNA’ or aberrant splicing byproducts, circRNAs have undergone a dramatic reappraisal and are now recognized as crucial regulatory molecules, abundantly expressed in eukaryotic cells and exhibiting notable tissue specificity. CircRNAs perform a wide range of regulatory functions, including acting as microRNA sponges, interacting with RNA-binding proteins, modulating transcription and splicing, and participating in protein translation. These diverse roles entail their significance in gene regulation. Increasing evidence links aberrant circRNA expression to the development and progression of various diseases. This review provides a comprehensive overview of the biogenesis, properties, and functional roles of circRNAs, with a specific focus on their involvement in malignancies—especially colorectal cancer (CRC), the third leading cause of cancer-related deaths worldwide. Aberrant circRNA expression has been documented in CRC tumor tissues, cells, blood, and extracellular vesicles, with individual circRNAs functioning either as oncogenes or tumor suppressors. Their dysregulation highlights their potential utility as biomarkers and therapeutic targets. This review further explores the clinical relevance and future applications of circRNAs in the early diagnosis, prognosis, and treatment of colorectal cancer and other malignancies.