Hepatitis B virus whole-X and X protein play distinct roles in HBV-related hepatocellular carcinoma progression.
Hepatitis B virus whole-X and X protein play distinct roles in HBV-related hepatocellular carcinoma progression.
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乙型肝炎病毒全X和X蛋白在HBV相关肝细胞癌进展中发挥不同作用
DOI：
10.1186/s13046-016-0366-3
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发表时间：
2016-06-03
期刊：
影响因子：
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通讯作者：
Liu J
中科院分区：
文献类型：
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作者：
Zhang Y;Liu H;Yi R;Yan T;He Y;Zhao Y;Liu J
背景HBV X蛋白（HBx）在肝细胞癌（HCC）发生发展中的作用已被广泛研究。然而，HBV全X蛋白（HBwx）是一种与HBx及其上游56个氨基酸融合的蛋白质，其在肝癌中的分子功能尚不清楚。本研究旨在探讨HBwx在肝癌发病机制中的分子功能，并对HBwx和HBx进行比较。方法采用免疫组织化学方法检测50例肝癌组织中HBwx和HBx的表达。通过动物模型和集落形成试验评价其成瘤能力。transwell法检测细胞的迁移和侵袭，GFP荧光法检测细胞的亚细胞定位。CCK-8法检测细胞增殖、细胞周期和凋亡;流式细胞仪检测细胞凋亡。结果HBwx在72%（36/50）的肝肿瘤组织中表达，主要表达于细胞核，并沉积于核膜周围的胞浆中。HBwx在体内和体外对肿瘤的发生和生长以及细胞的迁移和侵袭都有促进作用，但这种作用与HBx相比有所减弱。进一步分析表明，表达HBwx的细胞与表达HBx的细胞在细胞增殖、细胞周期和细胞凋亡方面存在差异。结论HBwx多出56个氨基酸，与肝癌的发生密切相关，但具有与HBx不同的生物学功能。
BackgroundThe role of HBV X protein (HBx) in the development of hepatocellular carcinoma (HCC) has been well studied. However, little is known about the molecular functions of HBV whole-X protein (HBwx), a protein fused with HBx and upstream 56 amino acid, in HCC. In current study, the molecular functions of HBwx in HCC pathogenesis has been investigated, as well as comparison between HBwx and HBx.MethodsExpression of HBwx and HBx in 50 HCC tissues was examined by immunohistochemistry. Their tumor-forming abilities were evaluated by an animal model and colony formation assay. Migration and invasion were detected by transwell assay and subcellular localization was tracked by GFP fluorescence. Cell proliferation, cell cycle and apoptosis were detected by CCK8 and FCM. Protein level was determined by Western blotting.ResultsHBwx was present in 72 % (36/50) of the liver tumor tissues and mainly expressed in the nucleus and deposited in the cytoplasm surrounding karyotheca. HBwx showed a promoting effect on tumorigenesis and growth in vivo and in vitro as well as cell migration and invasion, whilst such effect is compromised compared with that of HBx. Further analysis demonstrated differences in cell proliferation, cell cycle and cell apoptosis between cells expressing HBwx and those expressing HBx. Additionally, it was confirmed that RKIP-p-ERK pathway was involved in HBwx-related tumor formation.ConclusionHBwx, with the extra 56 amino acids, is closely related with hepatocarcinogenesis, while displays different biological functions from HBx.