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Rac3 regulates cell proliferation through cell cycle pathway and predicts prognosis in lung adenocarcinoma

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Tumor Biology

Abstract

Lung cancer is still the leading cause of malignant deaths in the world. It is of great importance to find novel functional genes for the tumorigenesis of lung cancer. We demonstrated that Rac3 could promote cell proliferation and inhibit apoptosis in lung adenocarcinoma cell line A549 previously. The aim of this study was to investigate the function and mechanism of Rac3 in lung adenocarcinoma cell lines. Immunohistochemistry staining was performed in 107 lung adenocarcinoma tissues and matched non-tumor tissues. Multivariate analysis and Kaplan-Meier analysis were used to investigate the correlation between Rac3 expression and the clinical outcomes. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and flow cytometry analysis were employed to determine the proliferative ability, cell cycle distribution, and apoptosis in H1299 and H1975 cell lines. Gene expression microarray and pathway analysis between the Rac3-siRNA group and the control group in A549 cells were performed to investigate the pathways and mechanism of Rac3 regulation. Rac3 was shown to be positively expressed in lung adenocarcinoma tissues, and the expression of Rac3 associates with longer survival in lung adenocarcinoma patients. Silencing of Rac3 significantly induced cell growth inhibition, colony formation decrease, cell cycle arrest, and apoptosis of lung adenocarcinoma cell lines, which accompanied by obvious downregulation of CCND1, MYC, and TFDP1 of cell cycle pathway involving in the tumorigenesis of lung adenocarcinoma based on the gene expression microarray. In conclusion, these findings suggest that Rac3 has the potential of being a therapeutic target for lung adenocarcinoma.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No. 30700821), the Liaoning Bai Qian Wan Talents Program (Grant No. 2011921038), the Liaoning Province Science and Technology (S&T) Project (Grant No. 2013225585), and the Liaoning Province Natural Science Foundation (Grant No. 2015020464).

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Authors and Affiliations

  1. Department of Thoracic Surgery, First Hospital of China Medical University, 155 Nanjingbei Street, Shenyang, Liaoning, 110001, China

    Gebang Wang, Huan Wang, Chenlei Zhang, Tieqin Liu & Hongxu Liu

  2. Department of Pathology, First Hospital of China Medical University, 155 Nanjingbei Street, Shenyang, Liaoning, 110001, China

    Qingchang Li & Xuyong Lin

  3. Department of Pathophysiology, College of Basic Medical Science, China Medical University, 77 Puhe Road, Shenyang, Liaoning, 110122, China

    Jingwei Xie

  4. Department of Thoracic Surgery, Beijing Tiantan Hospital, Capital Medical University, 6 Tiantan Xili, Dongcheng District, Beijing, 100050, China

    Hongxu Liu

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  1. Gebang Wang
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  2. Huan Wang
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Correspondence to Hongxu Liu.

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Wang, G., Wang, H., Zhang, C. et al. Rac3 regulates cell proliferation through cell cycle pathway and predicts prognosis in lung adenocarcinoma. Tumor Biol. 37, 12597–12607 (2016). https://doi.org/10.1007/s13277-016-5126-7

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  • DOI: https://doi.org/10.1007/s13277-016-5126-7

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