Abstract
Germline stem cell gene Piwil2 (piwi-like RNA-mediated gene silencing 2) is exclusively expressed in the testis and plays a critical role in gametogenesis through mediating Piwi-interacting RNA (piRNA) pathway. However, increasing data have suggested that this gene may play important roles as well in tumorigenesis. Piwil2 as a cancer-causing gene has been primarily considered as anonco gene that initiates or promotes tumorigenesis, but it de facto primarily be a tumor-barrier gene (TBG) that suppresses tumor initiation. The biological paradoxes might be related to its epigenetically alienated activation by intragenic promoter of Piwil2in the tumorigenic environments. The products of the alienated activation such as PL2L60 exhibits reversed Piwil2 function. The PL2L60 serves as tumor-initiating gene (TIG). In this review, we will summarize the current understanding of Piwil2 functions in the development and tumorigenesis and propose future directions for basic and translational research on Piwil2 in tumorigenesis. (Am J Transl Med 2017. 1:72- 95).