PiRNAs, PiRNA-Like, and PIWI Proteins in Somatic Cells: From Genetic Regulation to Disease Mechanisms.

PIWI-interacting RNAs (piRNAs) are small non-coding RNA molecules that were originally described as responsible for binding to PIWI proteins to silence transposons in the germline genome. Here we discuss their controversial influence in regulating gene expression in human somatic cells. Although their functions in human somatic cells remain controversial, current research has focused on their potential contribution to human diseases including cancers and cardiovascular diseases (CVDs). These small RNA molecules directly interact with PIWI proteins to form piRNA-induced silencing complexes (piRISC). These complexes regulate not only long non-coding RNAs (lncRNAs) but also mRNAs in their 3' untranslated region. The controversy in human somatic cells occurs because not all of the reports demonstrate a direct interaction between the small non-coding RNAs and the PIWI proteins and also whether these established complexes have silencing activities. Therefore, their importance in human physiology and pathology continues to remain controversial. Here we discuss the challenges and limitations that need to be addressed in order to establish and harness the potential of these ncRNAs in potential clinical applications. In this review, we distinguish those examples that have been shown to function as silencing complexes (piRNAs) from those that appear to be silencing complexes based only on their ability to bind to PIWI proteins (piRNA-like) in human somatic cells.