转录因子性别决定区Y框蛋白2在肝癌组织的表达及其对增殖及侵袭迁移能力的影响

Expression of sex determining region Y - box 2 in hepatocellular carcinoma tissues and effect on theSMMC- 7721 proliferation, invasion and migration

目的观察转录因子性别决定区Y框蛋白2（SOX2）在肝癌组织中的表达及其对肝癌细胞增殖、迁移及侵袭能力的影响。 方法利用免疫组织化学方法分析SOX2在32例肝癌及其癌旁组织中的表达；在肝癌细胞株SMMC-7721中通过细胞增殖、侵袭等功能实验分析SOX2通过上皮-间充质转化（EMT）促进转移复发的具体机制。 结果在人肝癌组织标本中SOX2较其配对癌旁组织及正常组织表达上调，其在癌组织、癌旁组织及正常肝组织中SOX2的阳性率分别为73.8%、32.5%及12.4%（P＝0.008、0.006）。在体外克隆形成实验结果示pWPI-SOX2转染组细胞克隆形成数为（654.9±39.4）个，显著高于对照组（232.7±19.4）个（P＝0.000）。Transwell小室实验结果显示它能促进肝癌细胞侵袭能力（P＝0.003）。慢病毒转染的SOX2高表达SMMC-7721肝癌细胞株发生EMT，上皮化表型E-钙黏蛋白（E-cadherin）、紧密连接蛋白（ZO-1）的表达下调和间质化表型N-钙黏蛋白（N-cadherin）和纤维连接蛋白（Fn）表达上调。 结论SOX2表达与肝癌的发生、发展密切相关，其具体机制可能是通过诱导EMT促进肝癌的转移复发。

ObjectiveTo investigate the association between the clinical significance and the expression of sex determining region Y-box 2 （SOX2） in hepatocellular carcinoma （HCC）, and to elucidate the its effect on proliferation, migration and invasion of SMMC-7721 cells. MethodsWe evaluated the clinical significance of SOX2 in 32 HCC patients using immunohistochemistry. The effects of SOX2 on the proliferation, invasion and migration of HCC cells were detected by clone formation and Transwell assay in vitro. ResultsThe expression of SOX2 was up-regulated in the human HCC tissues. The positive rate of SOX2 in cancer tissue, para cancer tissue and normal liver tissue was 73.8%, 32.5% and 12.4%, respectively （P=0.008, 0.006）. Clone formation experiment results showed that clone formation number of SOX2 overexpression cells （654.9±39.4） was significantly greater than that of control group （232.7±19.4, P=0.000）. In vitro, the characteristics of epithelial-mesenchymal transition （EMT） were induced by lentivirus transduction of SOX2 into SMMC-7721 cells, including the down-regulation of E-cadherin, and ZO-1, and the concomitant up-regulation of N-cadherin and Fibronectin. The overexpression of SOX2 in the HCC cell line promoted cell motility and invasion. ConclusionOur findings have uncovered a novel role for SOX2 in HCC metastasis, and provide a potential therapeutic target for HCC therapy.