Zhang Yu, Liu Hongli, Yi Ruitian, Yan Taotao, He Yingli, Zhao Yingren, Liu Jinfeng
Department of Infectious Diseases, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.
Department of Gastroenterology, Xi'an Central Hospital, Xi'an, 710003, Shaanxi Province, China.
J Exp Clin Cancer Res. 2016 Jun 3;35(1):87. doi: 10.1186/s13046-016-0366-3.
The 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.
Expression 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.
HBwx 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.
HBwx, with the extra 56 amino acids, is closely related with hepatocarcinogenesis, while displays different biological functions from HBx.
乙型肝炎病毒X蛋白（HBx）在肝细胞癌（HCC）发生发展中的作用已得到充分研究。然而，对于与HBx融合且包含上游56个氨基酸的乙型肝炎病毒全X蛋白（HBwx）在HCC中的分子功能却知之甚少。在本研究中，我们探究了HBwx在HCC发病机制中的分子功能，并对HBwx和HBx进行了比较。
采用免疫组织化学法检测50例HCC组织中HBwx和HBx的表达。通过动物模型和集落形成试验评估它们的致瘤能力。采用Transwell试验检测迁移和侵袭能力，通过绿色荧光蛋白（GFP）荧光追踪亚细胞定位。采用CCK8法和流式细胞术（FCM）检测细胞增殖、细胞周期和细胞凋亡。通过蛋白质印迹法测定蛋白质水平。
HBwx存在于72%（36/50）的肝肿瘤组织中，主要在细胞核中表达，并沉积在核膜周围的细胞质中。HBwx在体内外对肿瘤发生、生长以及细胞迁移和侵袭均有促进作用，但其作用与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。此外，证实RKIP-p-ERK信号通路参与了HBwx相关的肿瘤形成。
带有额外56个氨基酸的HBwx与肝癌发生密切相关，但其生物学功能与HBx不同。
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