Knockdown of COPS3 Inhibits Lung Cancer Tumor Growth in Nude Mice by Blocking Cell Cycle Progression.
Knockdown of COPS3 Inhibits Lung Cancer Tumor Growth in Nude Mice by Blocking Cell Cycle Progression.
复制标题
COPS3 的敲低通过阻断细胞周期进展抑制裸鼠肺癌肿瘤的生长
DOI：
10.7150/jca.16201
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发表时间：
2017
影响因子：
3.9
通讯作者：
Cui J
中科院分区：
文献类型：
--
作者：
Pang J;Yan X;Cao H;Qian L;He H;Tian H;Han F;Wang G;Chen X;Zhao Y;Hu JF;Cui J
COPS3 编码 COP9 信号体的第三个亚基，其异常表达与肺癌组织中的许多 RITE（“肿瘤表达增加区域”）基因相关。为了阐明COPS3在肺癌中的具体作用，我们通过免疫组织化学染色检查了其在肺癌组织中的表达。我们发现 COPS3 在大多数检查的肺癌样本中过度表达，特别是在小细胞癌和鳞状细胞癌中。 COPS3蛋白表达与Ki-67细胞增殖指数水平呈正相关（p=0.001），与肿瘤分化程度呈负相关（p=0.012）。在裸鼠异种移植肿瘤模型中，COPS3 的 shRNA 敲除显着减少了肿瘤生长。在肺腺癌 A549 细胞中，COPS3 的 shRNA 敲低通过上调细胞周期调节蛋白 P21 并下调细胞周期蛋白 B1 和 CDK4 诱导细胞周期停滞在 G0/G1 期。这些数据表明COPS3可能通过调节细胞周期相关蛋白来促进肿瘤生长。
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.