Piwi-interacting RNAs (piRNAs) and Cancer: Emerging Biological Concepts and Potential Clinical Implications

Piwi-interacting RNAs (piRNAs) are a very recently discovered class of small non-coding RNAs (ncRNAs), with approximately 20,000 piRNA genes already identified within the human genome. These short RNAs were originally described as key functional regulators for the germline maintenance and transposon silencing. However, due to our limited knowledge regarding their function, piRNAs were for a long time assumed to be the "dark matter" of ncRNAs in our genome. However, recent evidence has now changed our viewpoint of their biological and clinical significance in various diseases, as newly emerging data reveals that aberrant expression of piRNAs is a unique and distinct feature in many diseases, including multiple human cancers. Furthermore, their altered expression in cancer patients has been significantly associated with clinical outcomes, highlighting their important biological functional role in disease progression. Functionally, piRNAs maintain genomic integrity by silencing transposable elements, and are capable of regulating the expression of specific downstream target genes in a post-transcriptional manner. Moreover, accumulating evidences demonstrates that analogous to other small ncRNAs (e.g. miRNAs) piRNAs have both oncogenic and tumor suppressive roles in cancer development. In this article, we discuss emerging insights into roles of piRNAs in a variety of cancers, reveal new findings underpinning various mechanisms of piRNAs-mediated gene regulation, and highlight their potential clinical significance in the management of cancer patients.