miR-145-5p is associated with smoke-related chronic obstructive pulmonary disease via targeting KLF5

Increasing evidence illustrate that dysregulation of microRNAs (miRNAs) is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD), which is mainly resulted from cigarette smoke (CS) exposure. However, the role of miR-145-5p in CS-mediated COPD remains largely unknown. Thus, the aim of this study was to investigate the expression level of miR-145-5p in 31 human lung tissues samples, and to explore its regulatory role in the apoptosis and inflammation of human bronchial epithelial cells (HBECs) following CS extract (CSE) exposure. We found that miR-145-5p was significantly down-regulated in lung tissues from smokers without or with COPD compared to non-smokers. Functional assays showed that miR-145-5p overexpression remarkably alleviated CSE-induced apoptosis and inflammation response by regulating p53-mediated apoptotic signaling and pre-inflammatory factors such as necrosis factor-alpha (TNF-alpha), interleukins (IL)-6, IL-8 in HBECs, whereas, down-regulation of miR-145-5p showed opposite effects. Furthermore, luciferase reporter assays verified that Kruppel-like 5 (KLF5) was a direct target of miR-145-5p. Western blot assay also confirmed that KLF5 was up-regulated in COPD tissues and was negatively associated with miR-145-5p expression. Restoration of miR-145-5p expression significantly abrogated the suppressive effect of miR-145-5p on CSE-stimulated apoptosis and inflammation. In addition, the CSE-induced NF-kappa B signaling activation was suppressed by miR-145-5p overexpression. Therefore, our data suggested that miR-145-5p conferred protection against CSE-induced airway epithelial cell apoptosis and inflammation partially via targeting KLF5, which might be a potential therapeutic biomarker in COPD treatment.