Hepatitis B virus X protein upregulates survivin expression in hepatoma tissues
Hepatitis B virus X protein upregulates survivin expression in hepatoma tissues
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DOI：
10.1002/jmv.20466
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发表时间：
2005-11-01
影响因子：
12.7
通讯作者：
Ye, LH
中科院分区：
文献类型：
--
作者：
Zhang, XD;Dong, N;Ye, LH
B型肝炎病毒X蛋白（HBx）在肝细胞癌（HCC）的发生发展中起重要作用。探讨HBV抗原与凋亡抑制因子（IAP）家族在肝癌发生发展中的关系。应用免疫组化方法检测34例HCC和30例肝硬化组织中HBV抗原（HBsAg、HBcAg、HBxAg）和IAP家族成员（Survivin、XIAP、cIAP-1、cIAP-2）的表达水平。Survivin在三种组织类型中的阳性率均高于三种分子（P <0.05）。HBxAg和Survivin在HCC、癌旁组织和肝硬化组织中的阳性率分别为76.5%和88.2%、85.3%和91.2%、100%和93.3%，但Survivin和HBxAg的阳性率无显著性差异（均P> 0.05）。为了检测HBx对Survivin表达的影响，将编码HBx基因的质粒pCMV-X与编码Survivin基因的质粒pcDNA3-sur一起瞬时转染H7402肝癌细胞和L-O2人正常肝细胞。单独过表达HBx的细胞表现出凋亡增加以及存活素水平的剂量依赖性增加。而Survivin的共表达抑制了HBx诱导的细胞凋亡。为了研究HBx对肝癌细胞中生存素的影响，将质粒pCMV-X稳定转染人肝癌H7402细胞和L-O2细胞。这些H7402-X和L-O2-X细胞显示HBx和Survivin的高水平表达，但不显示凋亡。加入靶向HBx基因的RNAi载体pSilencer 3.0-X可降低H7402-X细胞中survivin蛋白的表达水平。总的来说，这些数据表明，HBx上调生存素在肝癌组织中的表达，这表明HBx和生存素可能都参与了肝癌的发生。
The hepatitis B virus X protein (HBx) plays an important role in the development of hepatocellular carcinoma (HCC). The relationship was examined between HBV antigens and IAP (inhibitor of apoptosis) family in development of HCC. The expression levels of HBV antigens (HBsAg, HBcAg, and HBxAg) and members of the IAP family (survivin, XIAP, clAP-1, and clAP-2) were detected immunohistochemically in tissues from 34 cases of HCC and 30 cases of liver cirrhosis. The positive rate of survivin was higher than these three molecules in all three tissue types (P < 0.05). The positive rates of HBxAg and survivin were high in HCC (76.5% and 88.2%), paratumor (85.3% and 91.2%), and liver cirrhosis (100% and 93.3%) tissues, with no significant differences between the survivin- and HBxAgpositive rates (each P > 0.05). To examine the effect of HBx on survivin expression, plasmid pCMV-X (encoding the HBx gene) was transfected transiently with or without plasmid pcDNA3-sur (encoding the survivin gene) into H7402 hepatoma cells and L-O2 human normal liver cells. Cells over-expressing HBx alone showed increased apoptosis along with a dose-dependent increase in survivin levels. However, co-expression of survivin inhibited the HBx-induced apoptosis. To examine the effect of HBx on survivin in hepatoma cells without apoptosis, plasmid pCMV-X was transfected stably into human hepatoma H7402 cells and L-O2 cells. These H7402-X and L-O2-X cells showed high-level expression of both HBx and survivin, but did not show apoptosis. The addition of pSilencer 3.0-X, an RNAi vector targeting the HBx gene reduced the expression levels of survivin protein in H7402-X cells. Collectively, these data demonstrate that HBx upregulates survivin expression in hepatoma tissues, suggesting that HBx and survivin may both be involved in carcinogenesis of HCC.