Ubiquitin specific peptidase 21 regulates interleukin-8 expression, stem-cell like property of human renal cell carcinoma.

USP family proteins play essential roles in cancer cell proliferation and apoptosis and represent as candidate targets for cancer therapeutics. However, the effects and underlying mechanism of USP21 on renal cell carcinomas (RCC) remain unclear. In the present study, we investigate the effects of USP21 on proliferation, invasion and cancer stem cells (CSCs) property of RCC cell lines. As a result, siRNA-mediated depletion of USP21 inhibits cell proliferation, invasion ability and decreases the CSCs percentage of RCC cell lines. Complementarily, forced expression of USP21 leads to increase of tumorigenic properties. In addition, CSCs properties assessed by sphere formation assays demonstrated that depletion of USP21 impair the self-renewal capability of CSCs. Furthermore, decrease USP21 levels is associated with repression of interleukin 8 (IL-8), a chemokine that regulates CSCs characteristics in RCC. Mechanistically, USP21 binds to the promoter region of IL-8 and mediates transcriptional initiation. These data suggest that USP21/IL-8 could be a pair of the critical molecular targets for the development of therapeutic strategies for RCC.