HES5通过激活STAT3促进细胞增殖和侵袭，并预示肝细胞癌患者预后不良。
HES5 promotes cell proliferation and invasion through activation of STAT3 and predicts poor survival in hepatocellular carcinoma.
作者信息
Zhu Guizhou, Shi Weidong, Fan Hui, Zhang Xiubing, Xu Jian, Chen Yongmei, Xu Zhiwei, Tao Tao, Cheng Chun
机构信息
Department of Medical College, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China.
Department of Medical Oncology, Nantong Second Peoples Affiliated Hospital of Nantong University, 43 Xinglong Road, Nantong 226001, Jiangsu Province, People's Republic of China.
出版信息
Exp Mol Pathol. 2015 Dec;99(3):474-84. doi: 10.1016/j.yexmp.2015.09.002. Epub 2015 Sep 3.
OBJECTIVES
HES5 is a member of the basic helix-loop-helix (bHLH) family of transcription factors, and involved in cell differentiation and proliferation in a variety of tissues other than HCC. Therefore, we have characterized HES5 and investigated its role during hepatocarcinogenesis.
METHODS
We first examined the expression of HES5 in eight paired frozen HCC and adjacent noncancerous liver tissues by Western blot. Immunohistochemistry was performed to confirm our results in 58 HCC samples and evaluated the relativity between the expression of HES5 and clinicopathological variables and estimated the prognostic significance. Moreover, Western blot examined the expression of downstream proteins by siRNA HES5. Flow cytometer assay was performed to investigate the role of HES5 in the process of HCC.
RESULTS
We found that HES5 was upregulated in HCC specimens. The data showed that high expression of HES5 was tightly associated with histological grade (P<0.01) and metastasis (P<0.01), and positively correlated with proliferation marker Ki-67 (P<0.01). Moreover, the results show that abnormal expression of HES5 influences cell growth and cell cycle of HCC cell lines. Furthermore, HES5 knockdown resulted in the reduction of p-STAT3.
CONCLUSION
These results suggested that suppression of the HES5 leading to inhibition of proliferation may be one of the mechanisms against HCC.
目的
HES5是转录因子碱性螺旋-环-螺旋（bHLH）家族的成员，参与除肝癌外多种组织中的细胞分化和增殖。因此，我们对HES5进行了表征，并研究了其在肝癌发生过程中的作用。
方法
我们首先通过蛋白质免疫印迹法检测了8对冷冻肝癌及癌旁非癌肝组织中HES5的表达。采用免疫组织化学方法在58例肝癌样本中证实我们的结果，并评估HES5表达与临床病理变量之间的相关性，以及估计其预后意义。此外，通过针对HES5的小干扰RNA（siRNA）利用蛋白质免疫印迹法检测下游蛋白的表达。采用流式细胞仪检测HES5在肝癌发生过程中的作用。
结果
我们发现HES5在肝癌标本中表达上调。数据显示，HES5的高表达与组织学分级（P<0.01）和转移（P<0.01）密切相关，且与增殖标志物Ki-67呈正相关（P<0.01）。此外，结果表明HES5的异常表达影响肝癌细胞系的细胞生长和细胞周期。此外，敲低HES5导致p-STAT3水平降低。
结论
这些结果表明，抑制HES5导致增殖受抑可能是对抗肝癌的机制之一。
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