PIWIL2 stabilizes β-catenin to promote cell cycle and proliferation in tumor cells.

PIWIL2 belongs to the PIWI protein subfamily and is widely expressed in a variety of tumors. Previous studies have shown that PIWIL2 has the characteristics of oncogene. Recently we reported that PIWIL2 suppresses GSK3β activity to regulate circadian rhythms through SRC-PI3K-AKT pathway. As GSK3β is a key part of the β-catenin destruction complex, it plays a vital role in regulating the degradation of β-catenin. Besides, the activated β-catenin/CyclinD1 pathway is involved in the proliferation of tumor cells. It is intriguing to investigate whether PIWIL2 regulates β-catenin and downstream pathway. In this study, we found that PIWIL2 suppressed GSK3β induced phosphorylation and ubiquitination of β-catenin, and thus increased β-catenin accumulation in the nucleus. By up-regulating β-catenin and CyclinD1, PIWIL2 can promote cell cycle and proliferation in tumor cells. Taken together, our results revealed a novel function of PIWIL2 in regulating β-catenin/CyclinD1 pathway in tumor cells, providing a new perspective for PIWIL2 as an oncogene.