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

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

doi:10.18632/oncotarget.9751

Liang Peng, Shunchang Jiao + Show 3 more

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https://doi.org/10.18632/oncotarget.9751

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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.

Highlights

Renal cell carcinoma (RCC) accounts for 90–95% of kidney malignancy, with estimations of 209,000 new patients and 102,000 deaths worldwide annually [1]
USP21 binds to the promoter region of interleukin 8 (IL-8) and mediates transcriptional initiation
We examined the mRNA expression of USP21 across five different renal cell carcinomas (RCC) cell lines and normal human kidney epithelial cell line HEK293T (Figure 1B and 1C)

Summary

Introduction

Renal cell carcinoma (RCC) accounts for 90–95% of kidney malignancy, with estimations of 209,000 new patients and 102,000 deaths worldwide annually [1]. There are three main different morphotypes of RCC, including clear cell RCC (85–90%) papillary RCC (6–15%) and chromophobe RCC (2–5%) [2]. About 20–30% of patients already show distant metastases at the time of diagnosis [3]. Surgical treatments are the only curative therapeutic approaches for early RCC [4]. The five-year survival rate of patients with RCC is relatively low [5]. Cancer stem-like cells (CSCs) are defined by their ability of tumor initiation, self-renewal and differentiation [6]. CSCs can survive chemotherapy and radiotherapy and are responsible for relapse after treatment and distant metastasis.

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