Dataset Information

ARFIP2 Regulates EMT and Autophagy in Hepatocellular Carcinoma in Part Through the PI3K/Akt Signalling Pathway.

ABSTRACT:

Purpose

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.

SUBMITTER: Huang K

PROVIDER: S-EPMC9789708 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

ARFIP2 Regulates EMT and Autophagy in Hepatocellular Carcinoma in Part Through the PI3K/Akt Signalling Pathway.

Huang Kaida K Lin Yubiao Y Wang Keyin K Shen Jianfen J Wei Dahai D

Journal of hepatocellular carcinoma 20221220

<h4>Purpose</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 36573219

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Project description:BackgroundIncreasing evidence has proven that the γ-secretase complex plays significant roles in the carcinogenesis of malignancies. However, the independent effect of nicastrin (NCSTN), the largest constituent of the γ-secretase complex, on the progression of hepatocellular carcinoma (HCC) remains to be discovered.MethodsIn our study, we used open online databases, including the Oncomine database, GEPIA and KMPlotter, to analyse the expression of 4 genes and their correlation with prognosis in HCC. NCSTN expression in 60 HCC patients from our centre was determined by immunohistochemical staining and qRT-PCR. The clinical and prognostic significance of NCSTN expression were analysed statistically. Stable Sk-hep1 cell lines with NCSTN overexpression were established using lentivirus-based vectors, and RNAi technology was used to transiently downregulate NCSTN expression in HepG2 cell lines. Cell growth and apoptosis were assessed by using EdU, clone formation, flow cytometry and Western blotting assays.ResultsBioinformatics analysis showed that NCSTN mRNA expression was generally higher in HCC tissues than in normal tissues according to a meta-analysis of 9 HCC datasets, excluding PS-1, PEN-2 and APH-1. Moreover, NCSTN was associated with a poor prognosis in HCC patients from The Cancer Genome Atlas (TCGA). Although the relationship between NCSTN levels and the clinicopathological features of HCC patients was not significant, a survival analysis of HCC patients from TCGA indicated that overall and disease-free survival were significantly associated with NCSTN expression. NCSTN expression in HCC cell lines regulated cell growth and apoptosis in vitro. NCSTN downregulation in HepG2 cells inhibited tumour growth ability in vivo. In addition, NCSTN downregulation in HepG2 cell lines decreased p-PI3K and p-Akt expression, and IGF1, a PI3K/Akt activator, neutralized the effects on PI3K and Akt phosphorylation. Moreover, NCSTN overexpression in Sk-hep1 cells activated the PI3K/Akt signalling pathway, and MK-2206, a PI3K/Akt inhibitor, reversed this activation according to Western blotting analysis.ConclusionsWe suggest that NCSTN serves as an oncogene in HCC by promoting growth and inhibiting apoptosis via the PI3K/Akt pathway, providing a potential novel therapeutic target for HCC treatment.

Dataset Information

ARFIP2 Regulates EMT and Autophagy in Hepatocellular Carcinoma in Part Through the PI3K/Akt Signalling Pathway.

Purpose

Methods

Results

Conclusion

Publications

ARFIP2 Regulates EMT and Autophagy in Hepatocellular Carcinoma in Part Through the PI3K/Akt Signalling Pathway.

Similar Datasets

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