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ARHGAP17 Inhibits Hepatocellular Carcinoma Progression by Inactivation of Wnt/β-Catenin Signaling Pathway

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Abstract

As a member of Rho GAPs family, Rho GTPase-Activating Protein 17 (ARHGAP17) regulates cytoskeletal recombination, cell polarity, cell proliferation and cell migration. ARHGAP17 is identified as a tumor suppressor in numerous cancer types. Current study intends to examine ARHGAP17 expression and its possible influence on the progression of hepatocellular carcinoma (HCC). ARHGAP17 expression in HCC cells was verified by RT-PCR and western blot. The proliferation and invasion of HCC cells were evaluated by CCK8 assay and transwell assay, respectively. The mRNA expression of ARHGAP17, PCNA, E-cadherin, N-cadherin, β-catenin, GSK-3β, Axin1, and APC were detected by RT-PCR. The protein expression of ARHGAP17, PCNA, E-cadherin, N-cadherin, β-catenin, p-β-catenin, GSK-3β, p-GSK-3β, Axin1, and APC were detected by western blot. ARHGAP17 staining was evaluated by immunohistochemistry and immunofluorescence. ARHGAP17 expression decreased significantly in HCC tumors and HCC cells after EMT. In response to overexpression of ARHGAP17, the capacities of HCC cell proliferation and invasion were reduced significantly, which were also confirmed by tumorigenesis experiments in vivo. With overexpression of ARHGAP17 in HCC cells, the p-GSK3β/GSK3β decreased, while the p-β-catenin/β-catenin, Axin1 and APC increased. In conclusion, ARHGAP17 inhibits HCC progression by inactivating the Wnt/β-catenin signaling pathway.

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All data generated or analyzed during this study are included in this published article.

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Funding

This work was supported by the Natural Science Foundation of Liaoning Province (2019-ZD-1062), the Joint Program of Key R&D Programs of Liaoning Province (2020JH2/10300168), Medical and Industrial Cross Joint Project of Liaoning Province (2022-YGJC-11) and the R&D Project for Major Technological Innovations of Shenyang City (19-112-4-081).

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Authors and Affiliations

  1. Graduate Training Base, General Hospital of Northern Theater Command of Jinzhou Medical University, Shenyang, 110016, Liaoning, China

    Sirui Fan

  2. Department of Hepatobiliary Surgery, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang, 110016, Liaoning, China

    Sirui Fan, Xing Chen, Mingjie Sun, Fengyang Chen, Chao Long, Yinghui Zhou, Boyuan Nan, Hao Zhao & Wei Zhang

  3. Graduate School, Jinzhou Medical University, Jinzhou, 121000, Liaoning, China

    Hongqing Zhao

  4. Department of Immunology, The College of Basic Medical Sciences, China Medical University, Shenyang, 110122, Liaoning, China

    Cheng Li

Authors
  1. Sirui Fan
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  2. Hongqing Zhao
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  3. Cheng Li
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  4. Xing Chen
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  5. Mingjie Sun
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  7. Chao Long
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  8. Yinghui Zhou
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  9. Boyuan Nan
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  10. Hao Zhao
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  11. Wei Zhang
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Contributions

HZ, SF, and WZ conceived and designed the experiments. CL, MS, FC analyzed the data. CL, YZ, BN, HZ performed the experiments. The manuscript was written by HZ, SF, and WZ. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Wei Zhang.

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The author reports no conflicts of interest in this work.

Ethical Approval

Current study was approved by the Ethics Committee of the General Hospital of Northern Theater Command of PLA.

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Written informed consent was obtained from the parents.

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Fan, S., Zhao, H., Li, C. et al. ARHGAP17 Inhibits Hepatocellular Carcinoma Progression by Inactivation of Wnt/β-Catenin Signaling Pathway. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10822-5

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