IMR Press / FBL / Volume 27 / Issue 3 / DOI: 10.31083/j.fbl2703089
Open Access Original Research
p62 Promotes Malignancy of Hepatocellular Carcinoma by Regulating the Secretion of Exosomes and the Localization of β-Catenin
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1 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 510120 Guangzhou, Guangdong, China
2 Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 510120 Guangzhou, Guangdong, China
3 Clinical Trial Institution of Pharmaceuticals, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 510120 Guangzhou, Guangdong, China
4 Department of Gastrointestinal Surgery, The Eighth Affiliated Hospital of Sun Yat-sen University, 518033 Shenzhen, Guangdong, China
5 Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, 510006 Guangzhou, Guangdong, China
*Correspondence: minjun@mail.sysu.edu.cn (Jun Min); liupq@mail.sysu.edu.cn (Peiqing Liu)
These authors contributed equally.
Academic Editor: Graham Pawelec
Front. Biosci. (Landmark Ed) 2022, 27(3), 89; https://doi.org/10.31083/j.fbl2703089
Submitted: 20 December 2021 | Revised: 21 February 2022 | Accepted: 24 February 2022 | Published: 8 March 2022
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: p62 is a multi-domain protein and participates in a variety of cellular biological activities. p62 is also related to tumor malignancy. However, the underlying molecular mechanism of p62 regulating the progression of hepatocellular carcinoma (HCC) remains unclear. Methods: The expression levels of p62 in HCC tissues and adjacent non-tumor tissues were confirmed using the TCGA dataset and immunohistochemistry. Stable p62-overexpressing HepG2 cells and p62-knockdown MHCC97H cells were established with lentiviral vectors. Cell proliferation, migration, and invasion assays were carried out to investigate the role of p62 in HCC cells and HCC-derived exosomes. The relationship between p62 and β-catenin was investigated by immunofluorescence and co-immunoprecipitation assays. Male nude mice (BALB/c-nu/nu) were used to establish the xenograft tumors. Results: We found that p62 was significantly upregulated in HCC, and a high level of p62 indicated the promotion of malignancy including cell proliferation, migration, and invasion. Exosomes derived from p62-overexpressing HepG2 also demonstrated the ability to promote tumor malignancy. Immunofluorescence and co-immunoprecipitation assays indicated that p62 interacts with β-catenin and regulates the localization of β-catenin to affect the intercellular junction. p62 also promotes tumor growth of HCC and down-regulates the expression of β-catenin in vivo. Conclusions: The results of this study concluded that p62 promotes the malignancy of HCC by regulating the secretion of exosomes and the localization of β-catenin. These findings may provide new ideas for the diagnosis and treatment of HCC.

Keywords
p62
β-catenin
hepatocellular carcinoma (HCC)
exosomes
malignancy
Figures
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