LncRNA MIR155HG contributes to smoke-related chronic obstructive pulmonary disease by targeting miR-128-5p/BRD4 axis

Jie Song,Qihu Wang,Liguo Zong

doi:10.1042/bsr20192567

Abstract

Chronic obstructive pulmonary disease (COPD) is a common airway disease characterized by an exaggerated pulmonary inflammatory response. Long noncoding MIR155 host gene (lncRNA MIR155HG) has been identified to be related to the macrophage polarization in COPD. However, the detailed function of MIR155HG in cigarette smoke (CS)-mediated COPD remains largely unknown. The expression level of MIR155HG was elevated while miR-218-5p was decreased in lung tissues of smokers without or with COPD, especially in smokers with COPD, and cigarette smoke extract (CSE)-treated human pulmonary microvascular endothelial cell (HPMECs) in a dose- and time-dependent manner. Then, functional experiments showed that MIR155HG deletion could reverse CSE exposure-induced apoptosis and inflammation in HPMECs. MiR-218-5p was confirmed to be a target of MIR155HG and rescue assay showed miR-218-5p inhibitor attenuated the inhibitory action of MIR155HG knockdown on CSE-induced HPMECs. Subsequently, miR-218-5p was found to target bromodomain containing 4 (BRD4) directly, and miR-218-5p overexpression overturned CSE-induced injury of HPMECs via regulating BRD4. Additionally, co-expression analysis indicated MIR155HG indirectly regulated BRD4 expression in HPMECs via miR-218-5p. Thus, we concluded that MIR155HG contributed to the apoptosis and inflammation of HPMECs in smoke-related COPD by regulating miR-128-5p/BRD4 axis, providing a novel insight on the pathogenesis of COPD and a therapeutic strategy on COPD treatments.

Highlights

Chronic obstructive pulmonary disease (COPD), a common airway disease, is characterized by chronic bronchiolitis and emphysema induced by the exaggerated pulmonary inflammatory response that was triggered by the interactions of genetic and environmental risk factors, and of which cigarette smoking (CS) is recognized as the best-defined risk factor and response to about 80–90% of the COPD cases [1,2]
We explored the expression patterns of MIR155HG in lung tissues of smokers without or with COPD and human pulmonary microvascular endothelial cell (HPMEC), identified the biological function of MIR155HG on HPMECs treated with cigarette smoke extract (CSE)
Pulmonary function values FEV1, FEV1/forced vital capacity (FVC) and FEV1% predicted were significantly lower in smokers with COPD than those in the smokers and non-smokers (P 0.05)

Summary

Introduction

Chronic obstructive pulmonary disease (COPD), a common airway disease, is characterized by chronic bronchiolitis and emphysema induced by the exaggerated pulmonary inflammatory response that was triggered by the interactions of genetic and environmental risk factors, and of which cigarette smoking (CS) is recognized as the best-defined risk factor and response to about 80–90% of the COPD cases [1,2]. CS can initiate pulmonary vascular impairment via directly injuring endothelial cells, result in the enhancement of cell apoptosis, reduced epithelial barrier formation and high levels of oxidative stress, leading to a sustained inflammatory response in the lung tissue [3,4,5]. LncRNAs have been identified to implicate in various physiological and pathological processes and to be dysregulated in various human diseases [7]. MicroRNA 155 host gene (MIR155HG), a novel identified lncRNA, encodes the microRNA (miR)-155, which regulates multiple signaling pathways of innate and adaptive immune

Methods

Results

Conclusion