Functions of exosome-derived noncoding RNA-encoded polypeptides/proteins in human diseases.

Exosomes are nanoscale vesicles that are ubiquitously present in biological fluids and exhibit remarkable stability, carrying a diverse array of biologically active molecules, including various RNAs, DNAs, and proteins. Exosomes are crucial mediators of intercellular signaling and exert extensive regulatory effects on nearly all physiological and pathological processes in the body. Traditionally, noncoding RNAs (ncRNAs) were deemed incapable of encoding proteins, but recent studies have demonstrated that noncoding RNAs harbor a substantial number of open reading frames, which possess the potential to encode peptides/proteins that are implicated in the pathogenesis and progression of various diseases. This review aims to comprehensively summarize the roles and mechanisms of exosome-derived ncRNA-encoded polypeptides/proteins (EDNEPs) in common diseases across nine major physiological systems, including the hematological, motor, digestive, respiratory, urinary, endocrine and reproductive, circulatory, immune, and nervous systems. Additionally, this review seeks to provide references for the clinical application of EDNEPs as diagnostic and prognostic biomarkers, promising therapeutic agents, and potential therapeutic targets.