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Published on: July 17, 2020
ARHGAP20 Expression Inhibited HCC Progression by Regulating the PI3K-AKT Signaling Pathway
Gao Liu1,2, Jia Li1,2, Cai-Yun Zhang1,2
1Department of Hepatobiliary Surgery, Meizhou People's Hospital, Meizhou, 514000, People's Republic of China.
Introduction:
One of the most common cancers is hepatocellular carcinoma (HCC), which is an aggressive cancer that is associated with high mortality. The expression and role of ARHGAP20 in HCC remain unclear.
Materials And Methods:
The expression and clinical role of ARHGAP20 were investigated using online databases and HCC samples from Meizhou People's Hospital. Wound healing assays, transwell migration/invasion assays, and lung metastasis models were performed using nude mice. Gene set enrichment analyses were used to further explore the potential mechanisms.
Results:
Inspired by expression analyses of three different public databases (ie, TIMER, Oncomine, and HCCDB database), we confirmed that ARHGAP20 was downregulated in clinical HCC tumors compared with normal controls. ARHGAP20 expression inhibited HCC migration and invasion in vitro and in vivo. Based on GSEA results, we tested markers of the PI3K-AKT signaling pathway. Interestingly, while ARHGAP20 upregulation suppressed HCC migration/invasion and phosphorylation of AKT/PI3K molecules, exposure to the PI3K-AKT pathway agonist rhIGF-1 partially rescued these phenomena. ARHGAP20 also showed a close correlation with certain components in the HCC immune microenvironment. Furthermore, we revealed that downregulated ARHGAP20 was significantly correlated with larger tumor size and vascular invasion, and could be used as an adverse independent prognostic factor for HCC OS but not RFS.
Conclusion:
ARHGAP20 was identified for the first time as a tumor suppressor gene that could inhibit HCC progression by regulating the PI3K-AKT signaling pathway and the immune microenvironment in HCC.
Insights
ARHGAP20 acts as a tumor suppressor in hepatocellular carcinoma (HCC), inhibiting cancer progression by regulating the PI3K-AKT pathway and immune microenvironment. Its downregulation is linked to poor prognosis in HCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Hepatocellular carcinoma (HCC) is a prevalent and aggressive cancer with high mortality.
- The role and expression of ARHGAP20 in HCC pathogenesis are not well understood.
Purpose of the Study:
- To investigate the expression and clinical significance of ARHGAP20 in HCC.
- To elucidate the underlying mechanisms by which ARHGAP20 influences HCC progression.
Main Methods:
- Analysis of ARHGAP20 expression in online databases and HCC patient samples.
- In vitro and in vivo assays (wound healing, transwell, metastasis models) to assess HCC cell migration and invasion.
- Gene Set Enrichment Analysis (GSEA) to explore signaling pathways, including PI3K-AKT.
Main Results:
- ARHGAP20 was found to be downregulated in HCC tumors compared to normal tissues.
- ARHGAP20 suppressed HCC cell migration and invasion in vitro and in vivo.
- Upregulation of ARHGAP20 inhibited PI3K-AKT signaling, which was partially reversed by rhIGF-1.
- ARHGAP20 expression correlated with the HCC immune microenvironment and served as an adverse prognostic factor for overall survival (OS).
Conclusions:
- ARHGAP20 functions as a tumor suppressor in HCC.
- ARHGAP20 inhibits HCC progression by modulating the PI3K-AKT pathway and the tumor immune microenvironment.
- Downregulated ARHGAP20 is associated with adverse clinical outcomes in HCC.
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