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

Liang Peng; Yi Hu; Demeng Chen; Shunchang Jiao; Shengkun Sun

doi:10.18632/oncotarget.9751

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Research Papers:

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

Liang Peng, Yi Hu, Demeng Chen, Shunchang Jiao and Shengkun Sun _

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Oncotarget. 2016; 7:42007-42016. https://doi.org/10.18632/oncotarget.9751

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Abstract

Liang Peng1,*, Yi Hu1,*, Demeng Chen2, Shunchang Jiao1, Shengkun Sun3

1Department of Oncology, Chinese PLA General Hospital, Beijing, China

2School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA

3Department of Urology, Chinese PLA General Hospital, Beijing, China

*These authors contributed equally to this work

Correspondence to:

Shengkun Sun, email: [email protected]

Keywords: USP21, renal cell carcinoma, cancer stem cell, IL-8

Received: February 23, 2016 Accepted: May 20, 2016 Published: May 31, 2016

ABSTRACT

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.

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Research Papers:

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

Abstract