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α干扰素抑制转染乙型肝炎病毒X基因表达慢病毒的Huh-7细胞的迁移和侵袭,并诱导抗病毒蛋白的表达。

Interferon-α inhibits cell migration and invasion and induces the expression of antiviral proteins in Huh-7 cells transfected with hepatitis B virus X gene-expressing lentivirus.

作者信息

Yang Qian, Li Xiao-Peng, Zhong Yuan-Bin, Xiang Tian-Xin, Zhang Lun-Li

机构信息

Department of Infectious Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.

出版信息

Exp Ther Med. 2017 Dec;14(6):5924-5930. doi: 10.3892/etm.2017.5288. Epub 2017 Oct 11.

DOI:10.3892/etm.2017.5288
PMID:29285141
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5740601/
Abstract

Hepatitis B virus (HBV) X protein (HBx) serves an important role in HBV infection and the development of HBV-related liver cancer. Interferon-α (IFN-α) is used to treat patients with HBV; however, the role of IFN-α in the development of HBV-related liver cancer remains unclear. The present study established a new HBV-related liver cancer model (Huh-7-HBx) by transfecting the hepatoma cell line Huh-7, with HBx-expressing lentivirus. Following IFN-α treatment, cell viability, migration and invasion, as well as the expression of antiviral proteins in Huh-7-HBx, were subsequently determined. The results demonstrated that HBx-expressing lentivirus had no significant effect on cell viability but promoted the migration and invasion of Huh-7 cells. The expression of the antiviral genes IFN α and β receptor subunit 1 (IFNAR1), IFNAR2, IFN-stimulated gene factor 3, double-stranded RNA-activated protein kinase and ribonuclease L, was also increased. Following treatment of Huh-7-HBx cells with IFN-α, the expression of antiviral genes was increased at the level of transcription and translation, whereas cell migration and invasion was decreased. The present study suggests that IFN-α may attenuate the development of HBV-related liver cancer by reducing cell migration and invasion and promoting the expression of antiviral proteins.

摘要

乙型肝炎病毒(HBV)X蛋白(HBx)在HBV感染及HBV相关肝癌的发生发展中发挥重要作用。干扰素-α(IFN-α)用于治疗HBV患者;然而,IFN-α在HBV相关肝癌发生发展中的作用仍不清楚。本研究通过用表达HBx的慢病毒转染肝癌细胞系Huh-7,建立了一种新的HBV相关肝癌模型(Huh-7-HBx)。在IFN-α处理后,随后测定了Huh-7-HBx细胞的活力、迁移和侵袭能力,以及抗病毒蛋白的表达。结果表明,表达HBx的慢病毒对细胞活力无显著影响,但促进了Huh-7细胞的迁移和侵袭。抗病毒基因IFNα和β受体亚基1(IFNAR1)、IFNAR2、IFN刺激基因因子3、双链RNA激活蛋白激酶和核糖核酸酶L的表达也增加。用IFN-α处理Huh-7-HBx细胞后,抗病毒基因的表达在转录和翻译水平均增加,而细胞迁移和侵袭能力则下降。本研究表明,IFN-α可能通过减少细胞迁移和侵袭并促进抗病毒蛋白的表达来减轻HBV相关肝癌的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fb/5740601/eac2c2e8fc94/etm-14-06-5924-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fb/5740601/ae0da17d19b5/etm-14-06-5924-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fb/5740601/eb123324be6e/etm-14-06-5924-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fb/5740601/80d960d42f53/etm-14-06-5924-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fb/5740601/53b98911f994/etm-14-06-5924-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fb/5740601/eac2c2e8fc94/etm-14-06-5924-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fb/5740601/ae0da17d19b5/etm-14-06-5924-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fb/5740601/eb123324be6e/etm-14-06-5924-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fb/5740601/80d960d42f53/etm-14-06-5924-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fb/5740601/53b98911f994/etm-14-06-5924-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fb/5740601/eac2c2e8fc94/etm-14-06-5924-g04.jpg

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本文引用的文献

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Chronic Hepatitis B Virus Infection: Disease Revisit and Management Recommendations.慢性乙型肝炎病毒感染:疾病再审视与管理建议
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STAT1 modification improves therapeutic effects of interferons on lung cancer cells.信号转导和转录激活因子1(STAT1)修饰可提高干扰素对肺癌细胞的治疗效果。
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Immunological aspects of antiviral therapy of chronic hepatitis B virus and hepatitis C virus infections.慢性乙型肝炎病毒和丙型肝炎病毒感染抗病毒治疗的免疫学方面
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HBx protein promotes oval cell proliferation by up-regulation of cyclin D1 via activation of the MEK/ERK and PI3K/Akt pathways.乙肝病毒X蛋白通过激活MEK/ERK和PI3K/Akt信号通路,上调细胞周期蛋白D1,从而促进卵圆细胞增殖。
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Inhibition of hepatitis B virus replication by ligand-mediated activation of RNase L.通过配体介导的RNase L激活抑制乙型肝炎病毒复制
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