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Theranostics 2020; 10(13):5998-6010. doi:10.7150/thno.43427 This issue Cite

Research Paper

Investigation of the role and mechanism of ARHGAP5-mediated colorectal cancer metastasis

Tian Tian1*, Zhan-Hong Chen1,2*, Zongheng Zheng2*, Yubo Liu1, Qi Zhao1, Yuying Liu1, Huijun Qiu1, Qian Long1, Miao Chen1, Liren Li1, Fangyun Xie1, Guangyu Luo1✉, Xiaojun Wu1✉, Wuguo Deng1✉

1. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
2. The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China
*These authors contributed equally to this article.

✉ Corresponding authors: Guangyu Luo, Sun Yat-Sen University Cancer Center, Guangzhou, China; E-mail: luogyorg.cn; or Xiaojun Wu, Sun Yat-Sen University Cancer Center, Guangzhou, China; E-mail: wuxjorg.cn; or Wuguo Deng, Sun Yat-Sen Un More

Citation:
Tian T, Chen ZH, Zheng Z, Liu Y, Zhao Q, Liu Y, Qiu H, Long Q, Chen M, Li L, Xie F, Luo G, Wu X, Deng W. Investigation of the role and mechanism of ARHGAP5-mediated colorectal cancer metastasis. Theranostics 2020; 10(13):5998-6010. doi:10.7150/thno.43427. https://www.thno.org/v10p5998.htm
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Abstract

Graphic abstract

Background: Metastatic colorectal cancer (CRC) is a lethal disease; however, the underlying molecular mechanisms remain unclear and require further study.

Methods: RNA-Seq, PCR, Western blotting, immunohistochemistry, ChIP and RNAi assays were performed to investigate Rho GTPase-activating protein 5 (ARHGAP5, aslo known as p190RhoGAP-B, p190-B) expression and the clinical relevance, functional roles and regulatory mechanisms of this protein using human CRC cells and tissues. In vivo, two cell-based xenograft models were used to evaluate the roles of ARHGAP5 in CRC metastasis.

Results: Here, we report that ARHGAP5 expression is significantly increased in metastatic CRC tissues and is inversely associated with patient overall survival. The suppression of ARHGAP5 reduces CRC cell metastasis in vitro and in cell-based xenograft models. Furthermore, we show that ARHGAP5 promotes CRC cell epithelial-mesenchymal transition by negatively regulating RhoA activity. Mechanistically, cAMP response element-binding protein (CREB1) transcriptionally upregulates ARHGAP5 expression, and decreased miR-137 further contributes to ARHGAP5 mRNA stability in CRC.

Conclusions: Overall, our study highlights the crucial function of ARHGAP5 in CRC metastasis, thus suggesting novel prognostic biomarkers and hypothetical therapeutic targets.

Keywords: colorectal cancer, tumor metastasis, ARHGAP5, CREB1, miR-137

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APA
Tian, T., Chen, Z.H., Zheng, Z., Liu, Y., Zhao, Q., Liu, Y., Qiu, H., Long, Q., Chen, M., Li, L., Xie, F., Luo, G., Wu, X., Deng, W. (2020). Investigation of the role and mechanism of ARHGAP5-mediated colorectal cancer metastasis. Theranostics, 10(13), 5998-6010. https://doi.org/10.7150/thno.43427.

ACS
Tian, T.; Chen, Z.H.; Zheng, Z.; Liu, Y.; Zhao, Q.; Liu, Y.; Qiu, H.; Long, Q.; Chen, M.; Li, L.; Xie, F.; Luo, G.; Wu, X.; Deng, W. Investigation of the role and mechanism of ARHGAP5-mediated colorectal cancer metastasis. Theranostics 2020, 10 (13), 5998-6010. DOI: 10.7150/thno.43427.

NLM
Tian T, Chen ZH, Zheng Z, Liu Y, Zhao Q, Liu Y, Qiu H, Long Q, Chen M, Li L, Xie F, Luo G, Wu X, Deng W. Investigation of the role and mechanism of ARHGAP5-mediated colorectal cancer metastasis. Theranostics 2020; 10(13):5998-6010. doi:10.7150/thno.43427. https://www.thno.org/v10p5998.htm

CSE
Tian T, Chen ZH, Zheng Z, Liu Y, Zhao Q, Liu Y, Qiu H, Long Q, Chen M, Li L, Xie F, Luo G, Wu X, Deng W. 2020. Investigation of the role and mechanism of ARHGAP5-mediated colorectal cancer metastasis. Theranostics. 10(13):5998-6010.

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