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Colorectal cancer (CRC) continues to be a substantial cause of cancer-related fatality globally, necessitating improved diagnostic and therapeutic strategies. Exosomes, small extracellular vesicles that facilitate intercellular communication, as key mediators in CRC progression by transporting bioactive molecules, including non-coding RNAs (ncRNAs). These exosomal ncRNAs (exo-ncRNAs) participate in regulating gene expression, tumor proliferation, metastasis, chemoresistance, and immune escape. Exo-ncRNAs show distinct patterns in CRC, making them potential non-invasive indicators for early detection and prognosis. Additionally, the potential of exosome-based therapies, including engineered exosomal RNA delivery, offers new avenues for precision oncology. However, addressing challenges, such as standardization of exosome isolation methods, clinical validation, and mechanistic elucidation, is necessary before their full clinical implementation. This article offers a comprehensive synthesis of the recent knowledge of exo-ncRNAs in CRC, emphasizing their biological functions, molecular mechanisms, and translational potential in diagnostics and therapeutics. Future research integrating artificial intelligence and multi-omics approaches may further enhance the clinical utility of exo-ncRNAs, advancing precision medicine in CRC management.
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