Zheng Bi-Yun, Fang Xue-Fen, Zou Lai-Yu, Huang Yue-Hong, Chen Zhi-Xin, Li Dan, Zhou Lin-Ying, Chen Hao, Wang Xiao-Zhong
Graduate School, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China.
Department of Gastroenterology, Union Hospital of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China.
Int J Oncol. 2014 Sep;45(3):1143-50. doi: 10.3892/ijo.2014.2499. Epub 2014 Jun 16.
HBx is a multifunctional regulator that interacts with host factors to contribute to the development of hepatocellular carcinoma. In this study, to explore the co-localization of HBx and COXIII in HepG2 cells and to investigate the molecular mechanism of HBx in HepG2 cell growth promotion, we first constructed a HepG2 cell line stably expressing the HBx gene in vitro by lentivirus vectors. In addition, we found that HBx co-localized with the inner mitochondrial protein, COXIII, in HepG2 cells by confocal laser scanning microscopy. It led to changes of mitochondrial biogenesis and morphology, including upregulation of COXIII protein expression, increased cytochrome c oxidase activity and higher mitochondrial membrane potential. The upregulation of COX-2 caused by HBx through generation of mitochondrial reactive oxygen species promoted cell growth. Thus, we conclude that co-localization of HBx and COXIII leads to upregulation of COX-2 that promotes HepG2 cell growth. Such a mechanism provides deeper insights into the molecular mechanism of HBV-associated hepatocellular carcinoma.
乙肝病毒X蛋白（HBx）是一种多功能调节因子，它与宿主因子相互作用，促进肝细胞癌的发展。在本研究中，为了探索HBx与细胞色素c氧化酶亚基III（COXIII）在肝癌细胞系HepG2中的共定位情况，并研究HBx促进HepG2细胞生长的分子机制，我们首先通过慢病毒载体在体外构建了稳定表达HBx基因的HepG2细胞系。此外，通过共聚焦激光扫描显微镜，我们发现HBx与线粒体内蛋白COXIII在HepG2细胞中共定位。这导致了线粒体生物合成和形态的变化，包括COXIII蛋白表达上调、细胞色素c氧化酶活性增加以及线粒体膜电位升高。HBx通过产生活性氧导致COX-2上调，进而促进细胞生长。因此，我们得出结论，HBx与COXIII的共定位导致COX-2上调，从而促进HepG2细胞生长。这种机制为乙型肝炎病毒相关肝细胞癌的分子机制提供了更深入的见解。
