ROS-Responsive miR-150-5p Downregulation Contributes to Cigarette Smoke-Induced COPD via Targeting IRE1.

MicroRNAs (miRNAs) have been reported in human diseases, in which chronic obstructive pulmonary disease (COPD) is included. Herein, we assessed the role along with the possible mechanisms of miR-150-5p in cigarette smoke- (CS-) induced COPD. The plasma miR-150-5p expression was lower in patients with COPD and acute exacerbation of COPD (AECOPD) and was related to disease diagnosis, disease severity, and lung function. Consistently, exposure to CS for 3 months or 3 days reduced miR-150-5p in the plasma and lung tissues of mice, and CS extract (CSE) inhibited miR-150-5p in human bronchial epithelial cells (HBECs) in a concentration along with time-dependent approach. In vitro, miR-150-5p overexpression decreased the contents of inflammatory factors interleukin- (IL-) 6, IL-8 along with cyclooxygenase-2 (COX-2), and endoplasmic reticulum (ER) stress markers glucose-regulated protein (GRP) 78 and C/-EBP homologous protein (CHOP) and promoted cell migrate. Mechanistically, miR-150-5p could bind with the 3'-untranslated region (UTR) of inositol requiring enzyme 1 (IRE1), while IRE1 overexpression obliterated the impacts of miR-150-5p. Besides, N-acetyl-cysteine (NAC) reversed CSE-induced miR-150-5p downregulation and its downstream effects. In vivo, miR-150-5p overexpression counteracted CS-triggered IRE1 upregulation, inflammation, and ER stress in the lung tissues of mice. In conclusion, our findings illustrated that ROS-mediated downregulation of miR-150-5p led to CS-induced COPD by inhibiting IRE1 expression, suggesting to serve as a useful biomarker for diagnosing and treating COPD.