Hepatitis B virus promotes hepatocellular carcinoma development by activating GP73 to repress the innate immune response.
Hepatitis B virus promotes hepatocellular carcinoma development by activating GP73 to repress the innate immune response.
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乙型肝炎病毒通过激活 GP73 抑制先天免疫反应促进肝细胞癌的发展
DOI：
10.1186/s13027-022-00462-y
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发表时间：
2022-10-04
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
B型肝炎病毒（HBV）在临床上引起急性和慢性感染。肝细胞癌（HCC）与HBV感染密切相关。血清高尔基体蛋白73（GP 73）在HBV感染时升高。然而，GP 73在HBV感染和HBV相关HCC发生中的作用仍然知之甚少。在这项研究中，HBV诱导的GP 73在调节肝癌发展中的潜在作用进行了研究。通过免疫组织化学、ELISA、Western印迹和定量实时PCR（qRT-PCR）分析评估HBV相关临床HCC组织和HBV感染的肝癌细胞和原代人肝细胞中GP 73的表达。通过流式细胞术、qRT-PCR、异种移植裸小鼠分析和球体形成测定来检测GP 73过表达细胞的致瘤性。通过Western印迹和qRT-PCR分析进一步研究GP 73和HBV感染对肝细胞中宿主先天免疫应答的影响。最初，我们证实HBV阳性的HCC组织中GP 73的表达显著增高。HBV基因的异位表达可以诱导GP 73在体外原代人肝细胞和肝癌细胞中的表达。此外，我们发现GP 73在正常肝细胞和肝癌细胞中促进HCC。我们还发现HBV基因的异位表达增加了GP 73的表达，抑制了宿主在肝细胞中的先天免疫反应。我们的研究结果表明，HBV通过激活GP 73来抑制宿主的先天免疫反应，从而促进肝癌的发展。这项研究增加了我们对HBV感染诱导的HCC发病机制的理解。这些发现还为GP 73作为潜在的HCC预防或治疗靶点提供了临床前支持。在线版本包含补充材料，可通过10.1186/s13027-022-00462-y获得。
Hepatitis B virus (HBV) causes acute and chronic infection in the clinic. Hepatocellular carcinoma (HCC) is closely linked to HBV infection. Serum Golgi protein 73 (GP73) increases during HBV infection. However, the role of GP73 during HBV infection and the occurrence of HBV-related HCC is still poorly understood. The underlying role of HBV-induced GP73 in regulating HCC development was investigated in this study. GP73 expression in HBV-related clinical HCC tissues and in HBV-infected hepatoma cells and primary human hepatocytes was evaluated by immunohistochemistry, ELISAs, Western blotting and quantitative real-time PCR (qRT-PCR) analysis. Tumorigenicity of GP73 overexpressed cells was detected by flow cytometry, qRT-PCR, xenograft nude mouse analyses and sphere formation assays. The effects of GP73 and HBV infection on host innate immune responses in hepatocytes were further investigated by Western blotting and qRT-PCR analysis. Initially, we confirmed that HBV-positive HCC tissues had significantly higher expression of GP73. Ectopic expression of the HBV gene could induce GP73 expression in primary human hepatocytes and hepatoma cells in vitro. In addition, we discovered that GP73 promotes HCC in both normal liver cells and hepatoma cells. We also found that ectopic expression of HBV genes increases GP73 expression, suppressing the host's innate immune responses in hepatocytes. Our results demonstrate that HBV facilitates HCC development by activating GP73 to repress the host's innate immune response. This study adds to our understanding of the pathogenesis of HBV infection-induced HCC. The findings also provide preclinical support for GP73 as a potential HCC prevention or treatment target. The online version contains supplementary material available at 10.1186/s13027-022-00462-y.
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影响因子：
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