J Cancer 2017; 8(7):1129-1136. doi:10.7150/jca.16201

Research Paper

Knockdown of COPS3 Inhibits Lung Cancer Tumor Growth in Nude Mice by Blocking Cell Cycle Progression

Jianan Pang1, Xu Yan2, He Cao1, Lei Qian1, Hua He1, Huimin Tian1, Fujun Han1, Guanjun Wang1, Xiao Chen1, Yuguang Zhao1, Ji-Fan Hu1, 3✉, Jiuwei Cui1✉

1. Cancer Center, the First Hospital of Jilin University, No. 71. Xinmin Street, Changchun, 130021, China;
2. Pathological diagnostic Center, the First Hospital of Jilin University, No.71.Xinmin Street, Changchun, 130021, China;
3. Stanford University Medical School, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.

Abstract

COPS3 encodes the third subunit of the COP9 signalosome and its aberrant expression is associated with many RITE (“Region of Increased Tumor Expression”) genes in lung cancer tissues. To elucidate the specific role of COPS3 in lung cancer, we examined its expression in lung cancer tissues by immunohistochemical staining. We found that COPS3 was overexpressed in most of the lung cancer samples examined, particularly in small cell carcinoma and squamous cell carcinoma. The expression of COPS3 protein was positively correlated with the level of Ki-67 cell proliferation index (p=0.001) and negatively related to the degree of tumor differentiation (p=0.012). In a xenograft tumor model in nude mice, shRNA-knockdown of COPS3 significantly reduced tumor growth. In lung adenocarcinoma A549 cells, shRNA-knockdown of COPS3 induced cell cycle arrest at G0/G1 phase by upregulating the cell cycle regulator protein P21 and downregulating cyclin B1 and CDK4. These data suggest that COPS3 may promote tumor growth by regulating cell-cycle associated proteins.

Keywords: Lung cancer, COPS3, gene expression, xenograft tumor, cell cycle.

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How to cite this article:
Pang J, Yan X, Cao H, Qian L, He H, Tian H, Han F, Wang G, Chen X, Zhao Y, Hu JF, Cui J. Knockdown of COPS3 Inhibits Lung Cancer Tumor Growth in Nude Mice by Blocking Cell Cycle Progression. J Cancer 2017; 8(7):1129-1136. doi:10.7150/jca.16201. Available from http://www.jcancer.org/v08p1129.htm