Long non-coding RNAs in the exosomal network: dual roles and clinical implications in cancer

Exosomes are a type of extracellular vesicles with a diameter of 30-150 nm, formed within multivesicular bodies of late endosomes, and released into the extracellular environment before being taken up by recipient cells. Exosomes transfer bioactive molecules, such as proteins and various RNAs, between cells and thereby influence recipient cell behavior. Among these molecules, long non-coding RNAs (lncRNAs) are not only selectively packaged into exosomes but have also been reported to participate in exosome biogenesis and secretion. Furthermore, they can contribute to cancer development by regulating gene expression through epigenetic mechanisms such as miRNA sponging, protein interactions, and methylation. These mechanisms appear to drive tumorigenesis by altering the tumor microenvironment, including macrophage polarization, immune evasion and suppression, angiogenesis, and lymphangiogenesis-mediated metastasis. In addition, exosomal lncRNAs can be readily detected in serum, highlighting their potential as biomarkers for liquid biopsy-based diagnosis. Finally, exosomal lncRNAs have been reported to contribute to drug resistance in various cancers. Therefore, therapeutic strategies targeting exosomal lncRNAs are expected to improve clinical outcomes in cancer patients.