Unveiling the functional paradigm of exosome-derived long non-coding RNAs (lncRNAs) in cancer: based on a narrative review and systematic review

Background and purpose The intricate mechanisms underlying intercellular communication within the tumor microenvironment remain largely elusive. Recently, attention has shifted towards exploring the intercellular signaling mediated by exosomal long non-coding RNAs (lncRNAs) within this context. This comprehensive systematic review aims to elucidate the functional paradigm of exosome-derived lncRNAs in cancer. Materials and methods The review provides a comprehensive narrative of lncRNA definition, characteristics, as well as the formation, sorting, and uptake processes of exosome-derived lncRNAs. Additionally, it describes comprehensive technology for exosome research and nucleic acid drug loading. This review further systematically examines the cellular origins, functional roles, and underlying mechanisms of exosome-derived lncRNAs in recipient cells within the cancer setting. Results The functional paradigm of exosome-derived lncRNAs in cancer mainly depends on the source cells and sorting mechanism of exosomal lncRNAs, the recipient cells and uptake mechanisms of exosomal lncRNAs, and the specific molecular mechanisms of lncRNAs in recipient cells. The source cells of exosomal lncRNAs mainly involved in the current review included tumor cells, cancer stem cells, normal cells, macrophages, and cancer-associated fibroblasts. Conclusion This synthesis of knowledge offers valuable insights for accurately identifying exosomal lncRNAs with potential as tumor biomarkers. Moreover, it aids in the selection of appropriate targeting strategies and preclinical models, thereby facilitating the clinical translation of exosomal lncRNAs as promising therapeutic targets against cancer. Through a comprehensive understanding of the functional role of exosome-derived lncRNAs in cancer, this review paves the way for advancements in personalized medicine and improved treatment outcomes.