Abstract
Renal cell carcinoma (RCC) is one of the commonest urological tumors. The incidence of RCC ranks third among urological tumors, after prostate cancer and bladder tumors. However, the etiology of RCC remains unclear. Ubiquitin-specific protease 22 (USP22), a potential marker of cancer stem cells, is associated with the occurrence and progression of numerous tumors. However, the roles of USP22 in RCC have not yet been investigated. Survivin is a member of the inhibitor of apoptotic protein family involved in RCC progression. The present study first detected the expression of USP22 and survivin in RCC tissues using immunohistochemistry and western blotting. It was revealed that the protein levels of USP22 and survivin in RCC tissues were higher than those in adjacent normal renal tissue. Subsequently, it was demonstrated that USP22 knockdown inhibited the growth of an RCC cell line ACHN and downregulated the protein level of survivin, accompanied by an increased level of cleaved-caspase-3. By contrast, overexpression of USP22 promoted the growth of ACHN cells, upregulated the expression of survivin and decreased the level of cleaved-caspase-3. Notably, the changes in USP22 expression did not affect the SURVIVIN mRNA level. Finally, it was confirmed that USP22 interacted with survivin and stabilized it by downregulating its ubiquitination. The present results indicate that USP22 may regulate survivin via deubiquitination, thereby promoting the proliferation of RCC cells. The results of the current study suggest that USP22 may represent a novel therapeutic target for patients with RCC.
Highlights
Renal cell carcinoma (RCC) is a common renal tumor in adults, accounting for ~90% of renal tumors and ~3% of all adult cancer cases, incidence rate of RCC was 5.78 per 100,000 women and 13.14 per 100,000 men in 2013 [1]
To determine whether the levels of Ubiquitin‐specific protease 22 (USP22) and survivin are clinically correlated with RCC, 10 pairs of tissues were collected, each consisting of a patient's RCC tissue and an adjacent normal tissue as the control (Table I)
The protein levels of USP22 and survivin in RCC were quantified with western blotting
Summary
Renal cell carcinoma (RCC) is a common renal tumor in adults, accounting for ~90% of renal tumors and ~3% of all adult cancer cases, incidence rate of RCC was 5.78 per 100,000 women and 13.14 per 100,000 men in 2013 [1]. The clinical onset of RCC is insidious; patients usually experience no obvious symptoms in the early stages. Survivin protein functions to inhibit caspase activation, thereby leading to negative regulation of apoptosis or programmed cell death [15]. The present study hypothesized that USP22 inhibits the apoptosis of renal carcinoma cells via modulating survivin level. This was first confirmed by immunohistochemical and western blotting that the protein levels of USP22 and survivin in RCC were higher compared with adjacent normal tissues. It was identified that USP22 upregulated survivin protein level and suppressed cell death via siRNA knockdown and overexpression experiments. The results of the present study revealed that USP22 may inhibit the apoptosis of RCC by deubiquitinating and stabilizing survivin
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
