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ARHGAP18 is Upregulated by Transcription Factor GATA1 Promotes the Proliferation and Invasion in Hepatocellular Carcinoma

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Abstract

Rho GTPase activating protein 18 (ARHGAP18), a member of the RhoGAP gene family that increases GTP hydrolysis and inhibits RhoGTPase, was recently discovered to play a role in the development of breast cancer. However, its exact biological role in hepatocellular carcinoma (HCC) remains unclear. In our present study, we comprehensively assessed ARHGAP18 expression and its correlation with the prognostic value of cancer patients in databases. Cell proliferation and colony formation assays were employed to monitor cell growth. Luciferase reporter assay, Chromatin immunoprecipitation qPCR (ChIP-qPCR), immunofluorescence were performed for mechanism research. The expression of genes and proteins was detected by real-time PCR and western blotting. According to the findings of this research, ARHGAP18 protein levels are increased in HCC tissues compared to adjacent nontumor tissues, and ARHGAP18 overexpression is associated with poor survival. The results of a gain- and loss-of-function experiment with HCC cells in vitro demonstrated that ARHGAP18 stimulated cell proliferation, migration, and invasion. Mechanistically, we found that the transcription factor GATA binding protein 1 (GATA1) could bind to the ARHGAP18 promoter and facilitate ARHGAP18 expression. Further studies revealed that the effects of ARHGAP18 silencing on HCCLM3 and Bel-7402 cells were blocked by GATA1 overexpression. In conclusion, GATA1-mediated ARHGAP18 up-regulation plays an important role in HCC tumorigenesis and might be a potential therapeutic target for HCC.

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Data Availability

The data of this paper is available from the corresponding author on reasonable request.

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Acknowledgements

We are grateful to all participants for their contributions to the present study.

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Authors and Affiliations

  1. Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tiyuanbei, Huanhuxi Road, Hexi District, Tianjin, 300060, People’s Republic of China

    Ping Chen, Xiaomeng Liu, Yayue Liu, Xu Bao & Qiang Wu

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  1. Ping Chen
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  2. Xiaomeng Liu
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  3. Yayue Liu
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  4. Xu Bao
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  5. Qiang Wu
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Contributions

PC and XL performed the experiments and data analysis. PC and QW conceived and designed the study. YL and XB did the analysis and interpretation of data. All authors read and approved the manuscript.

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Correspondence to Qiang Wu.

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Chen, P., Liu, X., Liu, Y. et al. ARHGAP18 is Upregulated by Transcription Factor GATA1 Promotes the Proliferation and Invasion in Hepatocellular Carcinoma. Appl Biochem Biotechnol 196, 679–689 (2024). https://doi.org/10.1007/s12010-023-04459-0

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