Parallel induction of cell proliferation and inhibition of cell differentiation in hepatic progenitor cells by hepatitis B virus X gene
Parallel induction of cell proliferation and inhibition of cell differentiation in hepatic progenitor cells by hepatitis B virus X gene
复制标题
乙型肝炎病毒X基因同时诱导肝祖细胞中的细胞增殖和抑制细胞分化。
DOI：
10.3892/ijmm.2012.1060
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发表时间：
2012-10-01
影响因子：
5.4
通讯作者：
Song, Fangzhou
中科院分区：
文献类型：
--
作者：
Huang, Jiayi;Shen, Lihong;Song, Fangzhou
越来越多的证据表明，正常干细胞可能通过充当癌症起始细胞而促进癌症的发展和进展。B型肝炎病毒X（HBX）蛋白与B型肝炎病毒（HBV）相关的肝癌发生有关。然而，HBX在肝祖细胞（HPC）中的作用知之甚少。在这项研究中，我们的目的是确定HBX在调节HPC增殖和分化的作用。用MTT法分析，我们发现，与表达绿色荧光蛋白（Ad-GFP）的腺病毒感染的HPC相比，表达HBX的腺病毒（Ad-HBX）感染的HPC生长更快。为了揭示HBX处理后细胞数量增加的机制，我们通过流式细胞术寻找细胞周期和凋亡的可能改变。我们发现HBX处理导致S期细胞周期分数增加和凋亡减少。此外，我们检查了用Ad-HBX感染的HPCs的分化，发现HBX在HP14.5细胞中的表达导致早期祖细胞标志物的表达增加和晚期肝细胞标志物的表达减少。此外，HBX抑制HP14.5细胞中的糖原合成，表明HBX能够抑制终末肝分化。因此，我们的研究结果强烈表明，HBX在调节HPC增殖和分化中起着重要作用。这是HBX介导的肝癌发生的潜在机制。
Increasing evidence has shown that normal stem cells may contribute to the development and progression of cancer by acting as cancer-initiating cells. The hepatitis B virus X (HBX) protein has been implicated in the hepatitis B virus (HBV)-associated liver carcinogenesis. However, the role of HBX in hepatic progenitor cells (HPCs) is poorly understood. In this study, we aimed to determine the role of HBX in regulating HPC proliferation and differentiation. Using MTT analysis, we showed that HPCs infected with adenovirus expressing HBX (Ad-HBX) grew more rapidly compared to HPCs infected with adenovirus expressing green fluorescent protein (Ad-GFP). To reveal the mechanism for the increased cell number after HBX treatment, we searched for possible alterations in the cell cycle and apoptosis by flow cytometry. We found that HBX treatment resulted in an increase in the S phase cell cycle fraction and a decrease in apoptosis. In addition, we examined the differentiation of HPCs infected with Ad-HBX and found that the HBX expression in HP14.5 cells led to an increased expression of early progenitor markers and a decreased expression of late hepatocyte markers. Furthermore, HBX inhibited glycogen synthesis in HP14.5 cells, indicating that HBX is capable of inhibiting terminal hepatic differentiation. Therefore, our results strongly suggest that HBX plays an important role in regulating HPC proliferation and differentiation. This is the potential mechanism of HBX-mediated liver carcinogenesis.