ARHGAP20 Expression Inhibited HCC Progression by Regulating the PI3K-AKT Signaling Pathway

Gao Liu; Jia Li; Cai-Yun Zhang; Dong-Yang Huang; Ji-Wei Xu

doi:10.2147/JHC.S298554

ARHGAP20 Expression Inhibited HCC Progression by Regulating the PI3K-AKT Signaling Pathway

J Hepatocell Carcinoma. 2021 Apr 21:8:271-284. doi: 10.2147/JHC.S298554. eCollection 2021.

Authors

Gao Liu^{1

2}, Jia Li^{1

2}, Cai-Yun Zhang^{1

2}, Dong-Yang Huang³, Ji-Wei Xu^{1

2}

Affiliations

¹ Department of Hepatobiliary Surgery, Meizhou People's Hospital, Meizhou, 514000, People's Republic of China.
² Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, People's Republic of China.
³ Center for Molecular Biology, Shantou University Medical College, Shantou, Guangdong, 515041, People's Republic of China.

Abstract

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.

Keywords: ARHGAP20; HCC; PI3K-AKT; immune microenvironment; progression.

Grants and funding

This work was supported by the training program of the Scientific Research of Meizhou People’s Hospital (Award Number PY-C2019004, PY-C2019002, PY-C2020019), the Guangdong Basic and Applied Basic Research Foundation, China (Grant No. 2019A1515110651, 2021A1515010902); and the China Postdoctoral Science Foundation (Grant no. 2020M672554).