Systematic investigation of biomarker-like role of ARHGDIB in breast cancer

Article type: Research Article

Authors: Wang, Xiaonan^{a; b; 1} | Bi, Xiaomin^{c; 1} | Huang, Xing^{d; 1; *} | Wang, Bijun^c | Guo, Qianying^c | Wu, Zhengsheng^{a; c; *}

Affiliations: [a] Department of Pathology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China | [b] Laboratory of Pathogenic Microbiology and Immunology, Anhui Medical University, Hefei, Anhui, China | [c] Department of Pathology, Anhui Medical University, Hefei, Anhui, China | [d] Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

Correspondence: [*] Corresponding authors: Xing Huang, Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310003, China. Tel.: +86 17816059169; E-mail: dr.huangxing@foxmail.com; Zhengsheng Wu, Department of Pathology, Anhui Medical University, Hefei, Anhui 230032, China. Tel.: +86 55162922879; E-mail: woozson@yahoo.com.

Note: [1] These authors contributed equally to this work.

Abstract: BACKGROUND: ARHGDIB, a Rho GDP dissociation inhibitor protein, has been reported playing critical roles in regulation of multiple biological responses. However, whether ARHGDIB serves as a valuable biomarker in cancer is little known so far, especially in breast cancer. OBJECTIVE: In this study, we aimed to investigate the importance of ARHGDIB in breast cancer, including but not limited to biomarker-like role, as well as potential mechanisms. METHODS: Total 100 breast cancer samples and 100 benign breast disease samples were enrolled and underwent detailed pathological assessment and IHC analysis. Human breast cancer cell lines and epithelial cell line were subjected to siRNA-mediated knock-down, RT-qPCR, western blot, MTT staining, cell cycle assay, transwell analysis respectively. RESULTS: We observed the expression of ARHGDIB is significantly higher in human breast cancer tissues compared with the benign tissues. ARHGDIB expression was positively correlated with tumor size, lymph node metastasis and TNM stage in breast cancer patients. Moreover, ARHGDIB depletion decreased proliferation, migration and invasion of breast cancer cells. Furthermore, we found ARHGDIB mediated epithelial-mesenchymal transition, and MMP2 is the key downstream effector of ARHGDIB. CONCLUSIONS: Hence, our results suggested the significance and predictive role of ARHGDIB in breast cancer. High expression of ARHGDIB indicated the poor prognosis for breast cancer patients.

Keywords: ARHGDIB, biomarker, breast cancer, EMT, prognosis

DOI: 10.3233/CBM-190562

Journal: Cancer Biomarkers, vol. 28, no. 1, pp. 101-110, 2020