PIWI-RNAs Small Noncoding RNAs with Smart Functions: Potential Theranostic Applications in Cancer

Simple Summary P-element-induced wimpy testis-interacting RNAs (piRNAs) are a novel class of small regulatory RNAs that often bind to PIWI proteins. First identified in animal germ line cells, piRNAs have key roles in germ line development. New insights into the functions of PIWI-piRNA complexes demonstrate that they regulate protein-coding genes. Aberrant piRNA expression has been also associated with different diseases, including cancer. Recently, piRNAs have been described in extracellular vesicles. EVs are one of the components of liquid biopsy, a revolutionary technique for detecting specific molecular biomarkers. This review focuses on piRNAs as potential biomarkers in different cancer types. Furthermore, piRNAs contained in extracellular vesicles could represent a new route for early diagnosis and therapies in a personalized medicine approach. P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a new class of small noncoding RNAs (ncRNAs) that bind components of the PIWI protein family. piRNAs are specifically expressed in different human tissues and regulate important signaling pathways. Aberrant expressions of piRNAs and PIWI proteins have been associated with tumorigenesis and cancer progression. Recent studies reported that piRNAs are contained in extracellular vesicles (EVs), nanosized lipid particles, with key roles in cell-cell communication. EVs contain several bioactive molecules, such as proteins, lipids, and nucleic acids, including emerging ncRNAs. EVs are one of the components of liquid biopsy (LB) a non-invasive method for detecting specific molecular biomarkers in liquid samples. LB could become a crucial tool for cancer diagnosis with piRNAs as biomarkers in a precision oncology approach. This review summarizes the current findings on the roles of piRNAs in different cancer types, focusing on potential theranostic applications of piRNAs contained in EVs (EV-piRNAs). Their roles as non-invasive diagnostic and prognostic biomarkers and as new therapeutic options have been also discussed.