title: Rac3 regulates cell proliferation through cell cycle pathway and predicts prognosis in lung adenocarcinoma.
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.
authors.affiliation: Department of Thoracic Surgery, First Hospital of China Medical University, 155 Nanjingbei Street, Shenyang, Liaoning, 110001, China.
authors.forename: Gebang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, First Hospital of China Medical University, 155 Nanjingbei Street, Shenyang, Liaoning, 110001, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, First Hospital of China Medical University, 155 Nanjingbei Street, Shenyang, Liaoning, 110001, China.
authors.forename: Chenlei
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, First Hospital of China Medical University, 155 Nanjingbei Street, Shenyang, Liaoning, 110001, China.
authors.forename: Tieqin
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Pathology, First Hospital of China Medical University, 155 Nanjingbei Street, Shenyang, Liaoning, 110001, China.
authors.forename: Qingchang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pathology, First Hospital of China Medical University, 155 Nanjingbei Street, Shenyang, Liaoning, 110001, China.
authors.forename: Xuyong
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Pathophysiology, College of Basic Medical Science, China Medical University, 77 Puhe Road, Shenyang, Liaoning, 110122, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Thoracic Surgery, First Hospital of China Medical University, 155 Nanjingbei Street, Shenyang, Liaoning, 110001, China. hongxuliucmu@163.com.|Department of Thoracic Surgery, Beijing Tiantan Hospital, Capital Medical University, 6 Tiantan Xili, Dongcheng District, Beijing, 100050, China. hongxuliucmu@163.com.
authors.forename: Hongxu
authors.initials: H
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D017209:Apoptosis; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D050680:Transcription Factor DP1 / Q000235:genetics; D020744:rac GTP-Binding Proteins / Q000032:analysis / Q000502:physiology*
chemical_list: C530104:CCND1 protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C411563:RAC3 protein, human; C493735:TFDP1 protein, human; D050680:Transcription Factor DP1; D019938:Cyclin D1; D020744:rac GTP-Binding Proteins
keywords: Apoptosis; Gene expression microarray; Lung adenocarcinoma; Proliferation; RNAi; Rac3