International Journal of COPD (Dec 2020)
MiR-218 Inhibits CSE-Induced Apoptosis and Inflammation in BEAS-2B by Targeting BRD4
Abstract
Xiaoli Liu,1 Junchen Wang,2,3 Huiling Luo,1 Chengxu Xu,1 Xingyu Chen,1 Rongxuan Zhang1 1Department of Respiratory, The Second People’s Hospital of Lanzhou City, Lanzhou City, Gansu Province, People’s Republic of China; 2Department of Interventional Medicine and Oncology, The Affiliated Hospital of Northwest Minzu University, Lanzhou City, Gansu Province, People’s Republic of China; 3Department of Interventional Medicine and Oncology, Gansu Second People ‘S Hospital, Lanzhou City, Gansu Province, People’s Republic of ChinaCorrespondence: Rongxuan ZhangDepartment of Respiratory, The Second People’s Hospital of Lanzhou City, No. 388 Jiangyuan Road, Chengguan District, Gansu Province 730030, People’s Republic of ChinaTel +86-18194260886Email [email protected]: Chronic obstructive pulmonary disease (COPD) is an age-related disease, and its incidence rate is increasing every year. MicroRNAs (miRNAs) play critical roles in the COPD process and function as key biomarkers or potential therapeutic targets for patients with COPD. However, the potential roles and functional effects of miR-218 in COPD remain undefined.Methods: The expression levels of miR-218 and bromodomain protein 4 (BRD4) were assessed by real-time quantitative polymerase chain reaction (RT-qPCR) or Western blot, respectively. In addition, a COPD cell model was established using cigarette smoke extract (CSE) in bronchial epithelial cell line (BEAS-2B). Enzyme-linked immunosorbent assay (ELISA) kit was applied to measure the concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) in cell supernatants of BEAS-2B cells. Moreover, cell apoptosis was examined by flow cytometry assay. The association relationship between miR-218 and BRD4 was confirmed by dual-luciferase reporter and RNA immunoprecipitation assay.Results: MiR-218 was downregulated in COPD and CSE-induced BEAS-2B cells, and it was positively correlated with forced expiratory volume in 1 second (FEV1) % in COPD patients. Mechanically, overexpression of miR-218 or knockdown of BRD4 mitigated apoptosis and inflammation in BEAS-2B cells induced by CSE. Additionally, overexpression of BRD4 weakened the miR-218-mediated effects on CSE-induced BEAS-2B cells.Conclusion: Overexpression of miR-218 inhibited CSE-induced apoptosis and inflammation in BEAS-2B cells by targeting BRD4 expression.Keywords: MiR-218, BRD4, COPD, cigarette smoke extract, COPD
