乙型肝炎病毒-X蛋白调节高迁移率族蛋白1以促进肝细胞癌的

StephenW

Oncol Lett. 2018 Oct;16(4):4418-4426. doi: 10.3892/ol.2018.9178. Epub 2018 Jul 19.
Hepatitis B virus-X protein regulates high mobility group box 1 to promote the formation of hepatocellular carcinoma.
Wu D1, Liang H1, Wang H1, Duan C1, Yazdani H1, Zhou J2, Pan Y2, Shan B1, Su Z1, Wei J1, Cui T1, Tai S1.
Author information
Abstract

Hepatitis B virus (HBV) infection is a risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) is an important carcinogen for HBV-induced HCC. When the HBx gene is integrated into the host cell genome, it is difficult to eradicate. The identification of an effective target to inhibit the oncogenic function of HBx is therefore critically important. The present study demonstrated that HBx, particularly truncated HBx, was expressed in several HBV-derived cell lines (e.g., Hep3B and SNU423). By analyzing data from The Cancer Genome Atlas, it was revealed that high expression of high mobility group box 1 (HMGB1) was associated with the process and prognosis of HCC. In vitro experiments confirmed that HBx could regulate the expression of HMGB1 and knockdown of HMGB1 could decrease the ability of HBx to promote cellular proliferation. HBx could also upregulate six transcription factors (GATA binding protein 3, Erb-B2 receptor tyrosine kinase 3, heat shock transcription factor 1, nuclear factor κB subunit 1, TATA-box binding protein and Kruppel-like factor 4), which could directly regulate HMGB1. By analyzing genes that are co-expressed with HMGB1, several signaling pathways associated with the development of HCC were identified. HBx and HMGB1 were revealed to be involved in these pathways, which may be the mechanism by which HBx promotes HCC by regulating HMGB1. These findings suggested that HMGB1 may be an effective target for inhibiting HBV-induced HCC.
KEYWORDS:

hepatitis B virus-X protein; hepatocellular carcinoma; high mobility group box 1

PMID:
    30214576
PMCID:
    PMC6126216
DOI:
    10.3892/ol.2018.9178

StephenW

Oncol Lett。 2018年10月; 16（4）：4418-4426。 doi：10.3892 / ol.2018.9178。 Epub 2018年7月19日。
乙型肝炎病毒-X蛋白调节高迁移率族蛋白1以促进肝细胞癌的形成。
吴D1，梁H1，王H1，段C1，亚兹达尼H1，周J2，潘Y2，山B1，苏Z1，魏J1，崔T1，泰S1。
作者信息
抽象

乙型肝炎病毒（HBV）感染是肝细胞癌（HCC）的危险因素。 HBV X蛋白（HBx）是HBV诱导的HCC的重要致癌物。当HBx基因整合到宿主细胞基因组中时，很难根除。因此，鉴定抑制HBx致癌功能的有效靶点至关重要。本研究证明HBx，特别是截短的HBx，在几种HBV衍生的细胞系（例如Hep3B和SNU423）中表达。通过分析癌症基因组图谱的数据，发现高迁移率族蛋白1（HMGB1）的高表达与HCC的过程和预后相关。体外实验证实，HBx可以调节HMGB1的表达，HMGB1的敲低可以降低HBx促进细胞增殖的能力。 HBx还可上调6种转录因子（GATA结合蛋白3，Erb-B2受体酪氨酸激酶3，热休克转录因子1，核因子κB亚基1，TATA-box结合蛋白和Kruppel样因子4），可直接调节HMGB1。通过分析与HMGB1共表达的基因，鉴定了与HCC发展相关的几种信号传导途径。 HBx和HMGB1被发现参与这些途径，这可能是HBx通过调节HMGB1促进HCC的机制。这些发现表明HMGB1可能是抑制HBV诱导的HCC的有效靶点。
关键词：

乙型肝炎病毒-X蛋白;肝细胞癌;高流动性组合框1

结论：
    30214576
PMCID：
    PMC6126216
DOI：
    10.3892 / ol.2018.9178

StephenW

www.spandidos-publications.com/10.3892/ol.2018.9178/download

newchinabok

StephenW 发表于 2018-9-15 16:57
www.spandidos-publications.com/10.3892/ol.2018.9178/download

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