title: RNA-binding motif protein 5 inhibits the proliferation of cigarette smoke-transformed BEAS-2B cells through cell cycle arrest and apoptosis.
abstract: Cigarette smoking has been shown to be the most significant risk factor for lung cancer. Recent studies have also indicated that RNA-binding motif protein 5 (RBM5) can modulate apoptosis and suppress tumor growth. The present study focused on the role of RBM5 in the regulation of cigarette smoke extract (CSE)-induced transformation of bronchial epithelial cells into the cancerous phenotype and its mechanism of action. Herein, we exposed normal BEAS-2B cells for 8 days to varying concentrations of CSE or dimethylsulfoxide (DMSO), followed by a recovery period of 2 weeks. Next, the RBM5 protein was overexpressed in these transformed BEAS-2B cells though lentiviral infection. Later, the morphological changes, cell proliferation, cell cycle, apoptosis, invasion and migration were assessed. In addition, we analyzed the role of RBM5 in xenograft growth. The expression of RBM5 along with the genes related to cell cycle regulation, apoptosis and invasion were also examined. Finally, our results revealed that BEAS-2B cells exposed to 100 µg/ml CSE acquired phenotypic changes and formed tumors in nude mice, indicative of their cancerous transformation and had reduced RBM5 expression. Subsequent overexpression of RBM5 in these cells significantly inhibited their proliferation, induced G1/S arrest, triggered apoptosis and inhibited their invasion and migration, including xenograft growth. Thus, we established an in vitro model of CSE-induced cancerous transformation and concluded that RBM5 overexpression inhibited the growth of these transformed cells through cell cycle arrest and induction of apoptosis. Therefore, our study suggests the importance of RBM5 in the pathogenesis of smoking-related cancer.
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Xue-Jiao
authors.initials: XJ
authors.lastname: Lv
authors.affiliation: Department of Pathology, College of Basic Medicine, Changchun University of Chinese Medicine, Changchun, Jilin 130117, P.R. China.
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Du
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Yu-Qiu
authors.initials: YQ
authors.lastname: Hao
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Zhen-Zhong
authors.initials: ZZ
authors.lastname: Su
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Li-Jing
authors.initials: LJ
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C473448:RBM5 protein, human; D016601:RNA-Binding Proteins; D025521:Tumor Suppressor Proteins