Li Yuehui, Yang Xiao Hui, Fang Shu Juang, Qin Chang Fei, Sun Rui Li, Liu Zhao Yang, Jiang Bin Yuan, Wu Xiang, Li Guancheng
Tumor Immunobiology Laboratory of the Cancer Research Institute, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Key Laboratory of Carcinogenesis, Ministry of Health, Central South University, Changsha, Hunan, P.R. China.
Xiangya Third Hospital, Central South University, Changsha, Hunan, P.R. China.
Oncol Rep. 2015 Feb;33(2):990-6. doi: 10.3892/or.2014.3668. Epub 2014 Dec 11.
HOX genes are transcription factors that control morphogenesis, organogenesis and differentiation. Increasing evidence suggests that HOX genes play a role in hepatocellular carcinoma (HCC) progression; however few studies have defined the functional roles and mechanisms of action. In the present study, we used siRNA and forced-expression in multiple cell lines to define the role of HOXA7 in the regulation of proliferation of HCC in vitro and in vivo. Knockdown of endogenous HOXA7 decreased the proliferation of HepG2 and QGY-7703 cells. These changes were not associated with significant changes in cyclin D1 and CDK4. However, downregulation of HOXA7 significantly reduced cyclin E1 and CDK2 protein levels. Conversely, overexpression of HOXA7 in QSG-7701 cells stimulated proliferation and increased cyclin E1 and CDK2 protein levels. Our results confirmed that HOXA7 promoted cell proliferation, and these changes were mediated by cyclin E1/CDK2. These observations contribute to our understanding of the important roles of HOXA7 in HCC development and progression and HOXA7 could be a promising molecular target for the development of new diagnostic and therapeutic strategies for HCC.
HOX基因是控制形态发生、器官发生和分化的转录因子。越来越多的证据表明，HOX基因在肝细胞癌（HCC）进展中发挥作用；然而，很少有研究明确其功能作用和作用机制。在本研究中，我们在多种细胞系中使用小干扰RNA（siRNA）和强制表达来确定HOXA7在体外和体内对HCC增殖调控中的作用。内源性HOXA7的敲低降低了HepG2和QGY-7703细胞的增殖。这些变化与细胞周期蛋白D1和细胞周期蛋白依赖性激酶4（CDK4）的显著变化无关。然而，HOXA7的下调显著降低了细胞周期蛋白E1和CDK2的蛋白水平。相反，在QSG-7701细胞中过表达HOXA7刺激了增殖并增加了细胞周期蛋白E1和CDK2的蛋白水平。我们的结果证实，HOXA7促进细胞增殖，且这些变化是由细胞周期蛋白E1/CDK2介导的。这些观察结果有助于我们理解HOXA7在HCC发生和进展中的重要作用，并且HOXA7可能成为开发HCC新诊断和治疗策略的有前景的分子靶点。
