Piwi proteins and their associated piRNAs are essential for preserving the self-renewal property of mammalian germ stem cells. Their highly conserved role in CpG island DNA methylation and chromatin modifications in germ stem cells has long been associated with transposon silencing but recent reports hint at protein coding regions being targets for Piwi-mediated epigenetic changes as well. Interestingly, the expression of PIWI family members is not restricted to the germline, and certain members have also been implicated in tumorigenesis in cases of adenocarcinomas, gliomas, and sarcomas. The following review discusses our knowledge of the function of Piwi proteins and piRNAs in suppressing transposable elements while maintaining the self-renewing population of germ stem cells. We also highlight the somatic function of Piwi as an epigenetic modifier. Furthermore, we summarize the recently uncovered involvement of Piwi proteins and piRNAs in various cancers.
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