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首页> 外文期刊>Virus Genes >Hepatitis B virus X protein upregulates transcriptional activation of human telomerase reverse transcriptase.
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Hepatitis B virus X protein upregulates transcriptional activation of human telomerase reverse transcriptase.

机译:乙型肝炎病毒X蛋白上调人类端粒酶逆转录酶的转录激活。

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摘要

It is well known that telomerase activation and virus infection are strongly associated with human hepatocellular carcinoma (HCC). Hepatitis B virus X protein (HBx) plays an important role in HCC pathogenesis. However, the mechanisms of HBx on telomerase activity are not well understood. To determine the potential roles of HBx in telomerase activity, both transfection and antisense assay were designed to examine the effects of HBx on telomerase in this report. Results showed that HBX gene increased telomerase activity and human telomerase reverse transcriptase (hTERT) expression in HBx-transfected cells and HBx-positive HCC samples. Co-transfection and luciferase reporter assay showed that HBx could stimulate hTERT promoter in a dose-dependent manner in different cells. Truncated and mutant reporter assays revealed that Sp1 binding sites mapped at -132 to +5 nt in hTERT promote were important for HBx-mediated upregulation of hTERT. Western blot did not show any change of Sp1 expression in HBx-transfected cells, but EMSA showed evidence of that HBx increased binding of Sp1 to its target DNA. These results provide new insights into the role of HBx in liver carcinogenesis.
机译:众所周知,端粒酶激活和病毒感染与人类肝细胞癌(HCC)密切相关。乙型肝炎病毒X蛋白(HBx)在HCC发病机理中起重要作用。但是,HBx对端粒酶活性的机制尚不清楚。为了确定HBx在端粒酶活性中的潜在作用,在本报告中设计了转染和反义分析来检查HBx对端粒酶的影响。结果显示,HBX基因在转染HBx的细胞和HBx阳性HCC样品中增加了端粒酶活性和人类端粒酶逆转录酶(hTERT)表达。共转染和荧光素酶报告基因检测表明,HBx可以在不同细胞中以剂量依赖性方式刺激hTERT启动子。截短的和突变的报告基因检测表明,hTERT中位于-132到+5 nt的Sp1结合位点促进了HBx介导的hTERT上调。 Western印迹未显示HBx转染细胞中Sp1表达的任何变化,但EMSA显示HBx增加Sp1与其靶DNA结合的证据。这些结果为HBx在肝癌发生中的作用提供了新的见解。

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