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Cavin1激活Wnt/β-连环蛋白信号通路以影响肝细胞癌的增殖和迁移。

Cavin1 activates the Wnt/β-catenin pathway to influence the proliferation and migration of hepatocellular carcinoma.

作者信息

Hao Xingyuan, Li Jinghua, Liu Bin, Jing Wei, Guo Yonghua, Liu Fusheng, Li Xiaomian, Chen Xi, Yuan Yufeng, Ma Weijie

机构信息

Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan Hubei, 430071, China; Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan, Hubei, P. R. China; The First Affiliated Hospital of Xi'an Jiao Tong University Yulin Hospital, Yulin, 719000, China.

Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan Hubei, 430071, China; Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan, Hubei, P. R. China.

出版信息

Ann Hepatol. 2024 Jan-Feb;29(1):101160. doi: 10.1016/j.aohep.2023.101160. Epub 2023 Sep 27.

Abstract

INTRODUCTION AND OBJECTIVES

Cavin1 is a cell membrane caveolin, with controversial function in different tumors. Meanwhile, the role of Cavin1 in hepatocellular carcinoma (HCC) progression remains unclear. In this study, we attempted to elucidate the significance of Cavin1 in HCC occurrence and progression.

MATERIALS AND METHODS

Cavin1 content was examined in HCC tissues and paired adjacent normal liver tissues by qRT-PCR and IHC among 81 HCC patients. The Cavin1-mediated regulation of HCC proliferation and metastasis was assessed through in vitro and in vivo experiments. Finally, using GSEA, we found out Cavin1 could be a potential regulator of the Wnt pathway. The alterations of the Wnt pathway-related proteins were identified by Western Blot analysis.

RESULTS

Cavin1 was lower expressed in HCC, which implied poor survival outcomes in HCC patients. Phenotypic experiments revealed that Cavin1 strongly suppressed HCC proliferation and migration in vitro and in vivo. Besides, altered epithelial-mesenchymal transition (EMT)-related protein expressions were detected. Based on our GSEA analysis, Cavin1 activated the Wnt pathway, and Western Blot analysis revealed diminished β-catenin, c-Myc, and MMP9 contents upon Cavin1 overexpression.

CONCLUSIONS

Cavin1 suppresses HCC progression by modulating HCC proliferation and migration via inhibiting the Wnt/β-catenin axis activation.

摘要

引言与目的

Cavin1是一种细胞膜小窝蛋白,在不同肿瘤中的功能存在争议。同时,Cavin1在肝细胞癌(HCC)进展中的作用仍不清楚。在本研究中,我们试图阐明Cavin1在HCC发生和进展中的意义。

材料与方法

通过qRT-PCR和免疫组化检测了81例HCC患者的HCC组织及配对的癌旁正常肝组织中的Cavin1含量。通过体外和体内实验评估了Cavin1介导的对HCC增殖和转移的调节作用。最后,利用基因集富集分析(GSEA),我们发现Cavin1可能是Wnt通路的潜在调节因子。通过蛋白质印迹分析确定Wnt通路相关蛋白的变化。

结果

Cavin1在HCC中低表达,这意味着HCC患者的生存结果较差。表型实验表明,Cavin1在体外和体内均强烈抑制HCC的增殖和迁移。此外,还检测到上皮-间质转化(EMT)相关蛋白表达的改变。基于我们的GSEA分析,Cavin1激活了Wnt通路,蛋白质印迹分析显示Cavin1过表达后β-连环蛋白、c-Myc和MMP9含量降低。

结论

Cavin1通过抑制Wnt/β-连环蛋白轴的激活来调节HCC的增殖和迁移,从而抑制HCC的进展。

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