Wang Qiuhong, Li Manhua, Zhang Xunlei, Huang Hua, Huang Jianfei, Ke Jing, Ding Haifang, Xiao Jinzhang, Shan Xiaohang, Liu Qingqing, Bao Bojun, Yang Lei
Department of Laboratory Medicine, Nantong Tumor Hospital, Nantong 226363, Jiangsu, China.
Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu, China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu, China.
Exp Mol Pathol. 2016 Jun;100(3):514-21. doi: 10.1016/j.yexmp.2016.05.001. Epub 2016 May 4.
CDK7 has been known as a component of CDK activating kinase (CAK) complex, the complex was composed of CDK7, Cyclin H and RING finger protein Mat1 that contribute to cell cycle progression by phosphorylating other CDKs. In addition, the complex is also an essential component of general transcription factor TFIIH which controls transcription via activating RNA polymerase II by serines 5 and 7 phosphorylation of the carboxyl-terminal domain (CTD) of its largest subunit. However, the role of CDK7 in the pathogenesis of gastric cancer has not been identified. Our study showed that CDK7 was significantly upregulated and positively correlated with tumor grade, infiltration depth, lymph node, Ki-67, and predicted poor prognosis in 173 gastric cancer specimens by immunohistochemistrical analyses. Furthermore, in vitro results indicated that CDK7 promoted proliferation of gastric cancer cells by CCK8, clone formation analyses and flow cytometric analyses, while CDK7 knockdown led to decreased cell proliferation. Our study will provide a theoretical basis for the study of CDK7 in gastric cancer.
细胞周期蛋白依赖性激酶7（CDK7）被认为是细胞周期蛋白依赖性激酶激活激酶（CAK）复合物的一个组成部分，该复合物由CDK7、细胞周期蛋白H和指环蛋白Mat1组成，通过磷酸化其他细胞周期蛋白依赖性激酶来促进细胞周期进程。此外，该复合物也是通用转录因子TFIIH的重要组成部分，TFIIH通过对其最大亚基羧基末端结构域（CTD）的丝氨酸5和7进行磷酸化来激活RNA聚合酶II，从而控制转录。然而，CDK7在胃癌发病机制中的作用尚未明确。我们的研究表明，通过免疫组织化学分析，在173例胃癌标本中，CDK7显著上调，且与肿瘤分级、浸润深度、淋巴结、Ki-67呈正相关，并预示预后不良。此外，体外实验结果表明，通过CCK8、克隆形成分析和流式细胞术分析，CDK7促进胃癌细胞增殖，而敲低CDK7则导致细胞增殖减少。我们的研究将为CDK7在胃癌中的研究提供理论依据。
