PIWI-interacting RNAs: Critical roles and therapeutic targets in cancer

P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a novel class of small regulatory RNAs (approximately 24–31 nucleotides in length) that often bind to members of the PIWI protein family. piRNAs regulate transposons in animal germ cells; piRNAs are also specifically expressed in many human tissues and regulate pivotal signaling pathways. Additionally, the abnormal expression of piRNAs and PIWI proteins has been associated with various malignant tumours, and multiple mechanisms of piRNA-mediated target gene dysregulation are involved in tumourigenesis and progression, suggesting that they have the potential to serve as new biomarkers and therapeutic targets for tumours. However, the functions and potential mechanisms of action of piRNAs in cancer have not yet been elucidated. This review summarises the current findings on the biogenesis, function, and mechanisms of piRNAs and PIWI proteins in cancer. We also discuss the clinical significance of piRNAs as diagnostic or prognostic biomarkers and therapeutic tools for cancer. Finally, we present some critical questions regarding piRNA research that need to be addressed to provide insight into the future development of the field.