PIWI-interacting RNAs in human cancer.

Abstract P-element-induced wimpy testis (PIWI) interacting RNAs (piRNAs) are a class of small regulatory RNAs mechanistically similar to but much less studied than microRNAs and small interfering RNAs. Today the best understood function of piRNAs is transposon control in animal germ cells, which has earned them the name ‘guardians of the germline’. Several molecular/cellular characteristics of piRNAs, including high sequence diversity, lack of secondary structures, and target-oriented generation seem to serve this purpose. Recently, aberrant expressions of piRNAs and PIWI proteins have been implicated in a variety of malignant tumors and associated with cancer hallmarks such as cell proliferation, inhibited apoptosis, invasion, metastasis and increased stemness. Researchers have also demonstrated multiple mechanisms of piRNA-mediated target deregulation associated with cancer initiation, progression or dissemination. We review current research findings on the biogenesis, normal functions and cancer associations of piRNAs, highlighting their potentials as cancer diagnostic/prognostic biomarkers and therapeutic tools. Whenever applicable, we draw connections with other research fields to encourage intercommunity conversations. We also offer recommendations and cautions regarding the general process of cancer-related piRNA studies and the methods/tools used at each step. Finally, we call attention to some issues that, if left unsolved, might impede the future development of this field.