Journal of Hepatocellular Carcinoma (Dec 2022)
ARFIP2 Regulates EMT and Autophagy in Hepatocellular Carcinoma in Part Through the PI3K/Akt Signalling Pathway
Abstract
Kaida Huang,1 Yubiao Lin,1 Keyin Wang,2 Jianfen Shen,3 Dahai Wei2– 4 1Department of Oncology, Xiamen Haicang Hospital, Xiamen, People’s Republic of China; 2Department of Infectious Diseases, Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China; 3Department of Central Laboratory, Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China; 4Institute of Hepatology, Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of ChinaCorrespondence: Dahai Wei, Institute of Hepatology, Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China, Tel/Fax +86-573-89975669, Email [email protected]: ARFIP2, a canonical BAR domain-containing protein, is closely associated with regulating cargo exit from the Golgi. However, the potential biological functions of ARFIP2 in hepatocellular carcinoma (HCC) have not been well investigated. This study aimed to explore the critical role of ARFIP2 in HCC cells.Methods: The expression of proteins related to epithelial to mesenchymal transition (EMT) and cell autophagy in HCC cells and tissues was assayed by quantitative real-time PCR, Western blotting, immunohistochemistry and immunofluorescence staining. The ability of cells to proliferate, migrate and invade was detected by Cell Counting Kit-8, Transwell migration and invasion assays. In addition, the function of ARFIP2 in vivo was assessed using a tumour xenograft model.Results: ARFIP2 expression is significantly upregulated in early recurrent and metastatic HCC patients and was positively correlated with a poor prognosis. ARFIP2 overexpression promoted cell proliferation, migration, and invasion by inducing EMT and inhibiting autophagy in vitro. Furthermore, the regulatory effects of ARFIP2 on autophagy and EMT were partially attributed to its regulation of the PI3K/AKT signalling pathway. The in vivo results also showed that ARFIP2 modulates HCC progression.Conclusion: Our results substantiate a novel mechanism by which ARFIP2 can regulate the activity/phosphorylation of Akt to promote EMT and inhibit autophagy in part via the PI3K/Akt signalling pathway. The ARFIP2/PI3K/Akt axis may be a potential diagnostic biomarker and therapeutic target for HCC.Graphical Abstract: Keywords: hepatocellular carcinoma, ARFIP2, PI3K/AKT, EMT, autophagy
