乙型肝炎病毒(HBV)感染与肝细胞癌(HCC)的发生具有十分密切的关系,乙肝病毒X蛋白(HBx)对HCC的发生和转移具有重要的作用.研究发现,骨桥蛋白(OPN)在许多肿瘤及其转移组织中高表达,与肿瘤转移密切相关.为了进一步阐明HBx在肝癌细胞迁移中的作用及其分子机制,以稳定表达HBx的肝癌细胞H7402-X为模型探讨了HBx与OPN的关系.结果发现,HBx可激活OPN启动子转录活性和上调OPN的mRNA表达."体外划痕"实验结果显示,HBx与肝癌细胞的迁移能力呈正相关.通过RNA干扰下调OPN的表达可抑制H7402-X细胞的迁移能力.本研究发现,HBx通过上调OPN的表达促进肝癌细胞迁移,对揭示肝癌转移的分子机制具有重要意义.
The close relationship of hepatitis B virus(HBV) infection with the development and metastasis of hepatocellular carcinoma(HCC) involves the crucial role of the HBV X gene(HBx).Osteopontin(OPN) was reported to play an important role in tumor cell adhesion,migration,invasion and angiogenesis.In the present study,we found that HBx was able to activate the promoter activity of OPN and up-regulate its mRNA level.The wound healing assay showed that the HBx-expression was related to the migration ability of hepatoma cells.The OPN-targeting small interference RNA(siRNA) could inhibit the migration of H7402-X cells.We conclude that the up-regulation of OPN is involved in HBx enhanced hepatoma cells migration.Our finding may provide further understanding about the molecular mechanism of HBx-related migration in hepatoma cells.