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[WISP-1:一种新型的乙型肝炎病毒相关肝细胞癌介质]

[WISP-1: a novel mediator of hepatitis B virus-related hepatocellular carcinoma].

作者信息

Jiang Xiang, Wang Zhi-Jun, Xie Qiong-Hui, Liu Qing, Lin Jiu-Sheng

机构信息

Gastro-intestinal Department, Zhongnan Hospital, Wuhan University, Wuhan 430071, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2013 Apr;21(4):285-9. doi: 10.3760/cma.j.issn.1007-3418.2013.04.011.

DOI:10.3760/cma.j.issn.1007-3418.2013.04.011
PMID:24021791
Abstract

OBJECTIVE

To explore the effect of hepatitis B virus (HBV) X protein (HBX) on expression of the host gene Wnt induced secreted protein-1 (WISP-1) that is related to the pathogenic process of hepatocellular carcinoma (HCC).

METHODS

Tumor and paratumor tissues were collected from HCC patients, and normal liver tissues were collected from healthy controls. Immunohistochemistry was used to evaluate the in vivo presence and expression levels of HBX and WISP-1 in the three tissue types. HepG2 cells stably transfected with pc-DNA3.1(+)-HBX or with pc-DNA3.1(+) only (G0, control) were generated and used to examine in vitro the HBX-induced changes in WISP-1 expression at the mRNA and protein levels by reverse transcription polymerase chain reaction and western blotting, respectively.

RESULTS

The HCC tissues showed significantly higher rates of positivity for WISP-1 expression than the non-tumor controls (76.6% vs. paratumor: 23.4% or normal tissues: 0%, x2= 35.967, P less than 0.01). HBX increased WISP-1 expression in HepG2 cells at both the mRNA (1170.33 +/- 41.26 vs. G0: 265.34 +/- 27.47, t = 31.63, P less than 0.01) and protein (240.33 +/- 11.37 vs. G0: 40.33 +/- 7.09, F = 600.57, P less than 0.01) levels.

CONCLUSION

HBV may up-regulate expression of the host gene WISP-1 through its X protein and thus promote the development of HCC.

摘要

目的

探讨乙型肝炎病毒(HBV)X蛋白(HBX)对宿主基因Wnt诱导分泌蛋白-1(WISP-1)表达的影响,该蛋白与肝细胞癌(HCC)的致病过程相关。

方法

收集HCC患者的肿瘤及癌旁组织,以及健康对照者的正常肝组织。采用免疫组织化学法评估三种组织类型中HBX和WISP-1的体内存在情况及表达水平。构建稳定转染pc-DNA3.1(+)-HBX或仅转染pc-DNA3.1(+)(G0,对照)的HepG2细胞,分别通过逆转录聚合酶链反应和蛋白质印迹法体外检测HBX诱导的WISP-1在mRNA和蛋白质水平的表达变化。

结果

HCC组织中WISP-1表达的阳性率显著高于非肿瘤对照(76.6% 对比癌旁组织:23.4% 或正常组织:0%,x2 = 35.967,P < 0.01)。HBX使HepG2细胞中WISP-1在mRNA(1170.33 ± 41.26对比G0:265.34 ± 27.47,t = 31.63,P < 0.01)和蛋白质(240.33 ± 11.37对比G0:40.33 ± 7.09,F = 600.57,P < 0.01)水平均升高。

结论

HBV可能通过其X蛋白上调宿主基因WISP-1的表达,从而促进HCC的发展。

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