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

被引:15
作者
Hong, Yang [1 ]
Huang, Xiaobo [1 ]
An, Lizhe [1 ]
Ye, Haiyun [1 ]
Ma, Kai [1 ]
Zhang, Fengshi [1 ]
Xu, Qingquan [1 ]
机构
[1] Peking Univ, Peoples Hosp, Dept Urol, Beijing, Peoples R China
关键词
COPS3; Prognosis; Proliferation; Carcinoma; Renal cell; PROGNOSTIC VALUE; SIGNALOSOME; ARABIDOPSIS; CANCER; PROTEIN;
D O I
10.1016/j.yexcr.2018.02.025
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:163 / 170
页数:8
相关论文
共 28 条
[1]  
Bech-Otschir D, 2002, J CELL SCI, V115, P467
[2]   The potential role of Akt phosphorylation in human cancers [J].
Cicenas, J. .
INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS, 2008, 23 (01) :1-9
[3]   Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 [J].
Ferlay, Jacques ;
Shin, Hai-Rim ;
Bray, Freddie ;
Forman, David ;
Mathers, Colin ;
Parkin, Donald Maxwell .
INTERNATIONAL JOURNAL OF CANCER, 2010, 127 (12) :2893-2917
[4]  
FERNANDESALNEMRI T, 1994, J BIOL CHEM, V269, P30761
[5]   VHL, the story of a tumour suppressor gene [J].
Gossage, Lucy ;
Eisen, Tim ;
Maher, Eamonn R. .
NATURE REVIEWS CANCER, 2015, 15 (01) :55-64
[6]   Role of the MPN subunits in COP9 signalosome assembly and activity, and their regulatory interaction with Arabidopsis cullin3-based E3 ligases [J].
Gusmaroli, Giuliana ;
Figueroa, Pablo ;
Serino, Giovanna ;
Deng, Xing Wang .
PLANT CELL, 2007, 19 (02) :564-581
[7]   Prognostic value of tissue-based biomarker signature in clear cell renal cell carcinoma [J].
Haddad, Ahmed Q. ;
Luo, Jun-Hang ;
Krabbe, Laura-Maria ;
Darwish, Oussama ;
Gayed, Bishoy ;
Youssef, Ramy ;
Kapur, Payal ;
Rakheja, Dinesh ;
Lotan, Yair ;
Sagalowsky, Arthur ;
Margulis, Vitaly .
BJU INTERNATIONAL, 2017, 119 (05) :741-747
[8]   p-AKT overexpression in primary renal cell carcinomas and their metastases [J].
Hager, Martina ;
Haufe, Heike ;
Lusuardi, Lukas ;
Schmeller, Nikolaus ;
Kolbitsch, Christian .
CLINICAL & EXPERIMENTAL METASTASIS, 2010, 27 (08) :611-617
[9]   COP9 signalosome function in the DDR [J].
Hannss, Ronny ;
Dubiel, Wolfgang .
FEBS LETTERS, 2011, 585 (18) :2845-2852
[10]   Treatment of Kidney Cancer Insights Provided by the VHL Tumor-Suppressor Protein [J].
Kaelin, William G., Jr. .
CANCER, 2009, 115 (10) :2262-2272