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Overexpression of COPS3 promotes clear cell renal cell carcinoma progression via regulation of Phospho–AKT(Thr308), Cyclin D1 and Caspase–3

ABSTRACT The third subunit of the COP9 signalosome (COPS3) is associated with cell proliferation and tumorigenesis process in cancer. The present study showed that the expression level of COPS3 was… Click to show full abstract

ABSTRACT The third subunit of the COP9 signalosome (COPS3) is associated with cell proliferation and tumorigenesis process in cancer. The present study showed that the expression level of COPS3 was upregulated in malignant cell lines and COPS3 overexpression was related with clinical stage, T stage, historical grade. Kaplan–Meier survival curves showed that COPS3 may function as a prognostic factor for overall survival. CCK–8 and colony formation assays revealed that knockdown of COPS3 in ACHN and 786–O significantly impacted proliferation in vitro. In addition, flow cytometry showed that inhibition of COPS3 induced G0/G1 arrest and promoted apoptosis. COPS3 may promote kidney cancer progression by altering Phospho–AKT(Thr308), Cyclin D1 and Caspase–3 expression. Collectively, Our findings suggest that COPS3 may be a new potential target of ccRCC. HIGHLIGHTSCOPS3 was overexpressed in ccRCC tissues and cell lines.Knockdown of COPS3 impaired the viability of ACHN and 786–O cells.si–RNA mediated downregulation of COPS3 induced G0/G1 phase and promoted apoptosis in ACHN and 786–O cells.Downregulation of COPS3 repressed Phospho–AKT(Thr308) and Cyclin–D1 expression and upregulated Caspase–3 expression.

Keywords: akt thr308; thr308 cyclin; cops3; phospho akt; cell

Journal Title: Experimental Cell Research
Year Published: 2018

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