由HERC4调控的SAV1可抑制肝细胞癌的增殖、迁移和侵袭。

SAV1, regulated by HERC4, inhibits the proliferation, migration, and invasion of hepatocellular carcinoma.

作者信息

Huang Fang, Tang Xujie, Sun Tao, Wang Gangyi, Ru Qingjing, Zheng Yi

机构信息

Department of Gastroenterology, Ningbo Fourth Hospital, Ningbo, China.

The second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, China.

出版信息

Transl Cancer Res. 2021 Jan;10(1):349-360. doi: 10.21037/tcr-20-698.

DOI:10.21037/tcr-20-698

PMID:35116265

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8799294/

Abstract

BACKGROUND

Hepatic carcinoma is one of the most malignant cancers worldwide. Salvador 1 (SAV1) plays a key role in a variety of human carcinogenesis. This study investigated the role of SAV1 and HERC4 in hepatocellular carcinoma (HCC).

METHODS

SAV1 and HERC4 expressions in HCC tissues were examined using RT-qPCR assay. The regulatory effect of HERC4 on SAV1 was verified by co-immunoprecipitation (Co-IP), RT-qPCR, Western blot, and immunofluorescent assays in HEP3B and Huh 7 cell lines. In addition, functional experimental verification was performed through Edu staining, colony formation, and Transwell assay. Finally, Xenograft tumor model was finally used in nude mice.

RESULTS

Clinical features showed significant difference with SAV1 and HERC4 expression. HERC4 was found to be upregulated, while SAV1 was downregulated in HCC. Patients with high HERC4 or low SAV1 had a worse prognosis. Results showed that HERC4 could notably decreased the expression level of SAV1 in HCC cells. Our results showed that overexpression HERC4 could reverse the inhibitory effects of SAV1 on HCC cell proliferation, migration, and invasion. SAV1 overexpression repressed tumor growth and enhance caspase 3 expression.

CONCLUSION

SAV1 can be directly downregulated by HERC4, indicating that the HERC4/SAV1 axis might have great promise for targeted therapies of HCC.

摘要

背景

肝癌是全球最恶性的癌症之一。Salvador 1（SAV1）在多种人类致癌过程中起关键作用。本研究调查了SAV1和HERC4在肝细胞癌（HCC）中的作用。

方法

采用RT-qPCR检测HCC组织中SAV1和HERC4的表达。通过共免疫沉淀（Co-IP）、RT-qPCR、蛋白质免疫印迹法和免疫荧光法在HEP3B和Huh 7细胞系中验证HERC4对SAV1的调节作用。此外，通过Edu染色、集落形成和Transwell实验进行功能实验验证。最后，在裸鼠中建立异种移植瘤模型。

结果

临床特征显示SAV1和HERC4表达存在显著差异。发现HCC中HERC4上调，而SAV1下调。HERC4高表达或SAV1低表达的患者预后较差。结果表明，HERC4可显著降低HCC细胞中SAV1的表达水平。我们的结果表明，过表达HERC4可逆转SAV1对HCC细胞增殖、迁移和侵袭的抑制作用。SAV1过表达抑制肿瘤生长并增强半胱天冬酶3的表达。