Hepatitis C Virus F Protein Up-Regulates c-myc and Down-Regulates p53 in Human Hepatoma HepG2 Cells
Hepatitis C Virus F Protein Up-Regulates c-myc and Down-Regulates p53 in Human Hepatoma HepG2 Cells
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DOI：
10.1159/000107271
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发表时间：
2007-08
期刊：
影响因子：
4.6
通讯作者：
Wen-Bin Wu;Sheng-wen Shao;Lan‐juan Zhao;Jie Luan;Jie Cao;Jun Gao;Shi-ying Zhu;Z. Qi
中科院分区：
文献类型：
--
作者：
Wen-Bin Wu;Sheng-wen Shao;Lan‐juan Zhao;Jie Luan;Jie Cao;Jun Gao;Shi-ying Zhu;Z. Qi
目的：丙型肝炎病毒（HCV） F蛋白是一种新发现的蛋白，由+1重叠核心编码基因的替代开放阅读框编码。研究发现HCV核心蛋白对c-myc和p53基因的调控参与了肝癌的发生。我们想知道HCV F蛋白是否对c-myc和p53基因的转录产生类似或不利的调节作用。方法：构建含HCV F基因的质粒pcDNA3.1-F和含HCV核心基因pcDNA3.1-C，瞬时转染HepG2细胞。采用实时荧光定量PCR或Western blotting检测c-myc和p53基因转录或翻译水平的变化。结果：pcDNA3.1-F转染的细胞c-myc转录水平明显高于未转染质粒的细胞。而转染pcDNA3.1-F的细胞中p53转录水平低于亲本细胞。此外，HCV F蛋白上调了c-myc表达水平，下调了p53表达水平。结论：HCV F蛋白在细胞癌基因c-myc和抗癌基因p53中具有调控特性，可能参与肝细胞癌的形成。
Objectives: Hepatitis C virus (HCV) F protein is a newly identified protein encoded by an alternative open reading frame that +1 overlaps core-encoding gene. It has been found that regulation of c-myc and p53 genes by HCV core protein is involved in liver cancer genesis. We wondered whether HCV F protein exerts similar or adverse regulatory effects on the transcription of c-myc and p53 genes. Methods: HCV F gene-containing, plasmid pcDNA3.1-F and HCV core gene-containing pcDNA3.1-C were constructed and transiently transfected into HepG2 cells. Real-time quantitative PCR or Western blotting was used to determine the changes at transcription or translation levels of c-myc and p53 genes. Results: The transcription level of c-myc was much higher in pcDNA3.1-F transfected cells than those without plasmid transfected. Whereas the level of p53 transcription in pcDNA3.1-F transfected cells was lower than those in the parental cells. Moreover, levels of c-myc expression were up-regulated and those of p53 expression were down-regulated by HCV F protein. Conclusions: HCV F protein is of regulatory properties in cellular oncogene c-myc and anti-oncogene p53, which may be implicated in the formation of hepatocellular carcinoma.