HBx通过HIPPO信号通路导致小鼠肝癌的发生机制

张思遥; 黄欣; 王薛; 杜彬; 毋楠; 周梦瑶; 冯涛

doi:10.16016/j.1000-5404.201910202

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HBx通过HIPPO信号通路导致小鼠肝癌的发生机制

基础医学 | 更新时间：2026-01-09

- HBx通过HIPPO信号通路导致小鼠肝癌的发生机制
- Hepatitis B virus X promotes tumorigenesis of hepatocellular carcinoma through HIPPO signaling pathway in mice
- 第三军医大学学报 2020年42卷第7期页码：664-670
- 作者机构：
  
  400016 重庆，重庆医科大学分子医学与肿瘤研究中心，基础医学院生物化学与分子生物研究中心
- 作者简介：
  
  [冯涛，E-mail: 100733@cqmu.edu.cn FENG Tao, E-mail: 100733@cqmu.edu.cn
- 基金信息：
  
  国家自然科学基金面上项目(81071770)
- DOI：10.16016/j.1000-5404.201910202
  中图分类号： R372.1;R730.23;R735.7
- 收稿：2019-10-30，
  
  修回：2019-11-30，
  
  纸质出版：2020-04-15
- 稿件说明：
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张思遥, 黄欣, 王薛, 等. HBx通过HIPPO信号通路导致小鼠肝癌的发生机制[J]. 第三军医大学学报, 2020,42(7):664-670.

Siyao ZHANG, Xin HUANG, Xue WANG, et al. Hepatitis B virus X promotes tumorigenesis of hepatocellular carcinoma through HIPPO signaling pathway in mice[J]. Journal of Third Military Medical University, 2020, 42(7): 664-670.
张思遥, 黄欣, 王薛, 等. HBx通过HIPPO信号通路导致小鼠肝癌的发生机制[J]. 第三军医大学学报, 2020,42(7):664-670. DOI： 10.16016/j.1000-5404.201910202.

Siyao ZHANG, Xin HUANG, Xue WANG, et al. Hepatitis B virus X promotes tumorigenesis of hepatocellular carcinoma through HIPPO signaling pathway in mice[J]. Journal of Third Military Medical University, 2020, 42(7): 664-670. DOI： 10.16016/j.1000-5404.201910202.

摘要

目的

观察HIPPO信号通路在小鼠感染乙型肝炎病毒X(hepatitis B virus X，HBx)不同时间的变化，初步探讨HBx导致肝癌发生的机制。

方法

将转染HBx的肝前体细胞通过门静脉注射入小鼠体内，构建能稳定表达HBx的动物模型，分别于30、90、180、360 d取肝脏组织，HE染色观察肝脏组织病理特征，RT-PCR、Western blot以及免疫组化法检测肝脏组织中HBx的表达，RT-PCR检测HIPPO信号通路相关因子MST1、YAP1 mRNA的表达，Western blot检测MST1、YAP1、p-MST1、p-YAP1蛋白的表达。

结果

成功构建能在小鼠肝脏中稳定表达HBx的动物模型并发展为肝癌，Western blot结果显示，与对照组相比，HBx组小鼠肝脏组织在术后30 d即出现MST1表达下调，p-MST1表达上调(

0.01)；YAP1表达上调，p-YAP1表达下调(

0.05)，RT-PCR与Western blot结果一致。这种改变一直持续至肿瘤发生。

结论

HBx可以导致小鼠肝癌发生，其机制可能与长期影响HIPPO信号通路的表达有关。

Abstract

Objective

To explore the changes in HIPPO signaling pathway in mouse liver tissues expressing hepatitis B virus X protein (HBx) and explore the mechanism of HBx for causing hepatocellular carcinoma (HCC).

Methods

Immortalized murine liver progenitor cells transfected with HBx gene were injected in mice

via

the hepatic portal vein. At 30

180

and 360 d after the cell injection

the liver tissues of the mice were sampled to examine HBx expression using real-time PCR

Western blotting and immunohistochemistry; the expression levels of the key factors in the HIPPO signaling pathway (MST1

YAP1

p-MST1

and p-YAP1) were detected using real-time PCR and Western blotting.

Results

We successfully established a mouse model with HBx expression in the liver tissues. The results of both real-time PCR and Western blotting showed that the expression levels of MST1 and p-YAP1 were down-regulated and YAP1 and p-MST1 were up-regulated in the liver tissues of the mouse model

and such changes persisted till the occurrence of HCC.

Conclusion

HBx causes HCC in mice possibly by persistently affecting HIPPO signaling pathway.

关键词

Keywords

references

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