Let-7c-5p Protects Against Cigarette Smoke-induced Chronic Obstructive Pulmonary Disease

BackgroundMicroRNAs(miRNAs)have been revealed to be associated with the pathogenesis and progression of cigarette smoking induced chronic obstructive pulmonary disease(COPD).However,the role of Let-7c-5p in CS-mediated COPD remains largely vague.MethodThe expression levels of Let-7c-5p and Rac Family Small GTPase 1(RAC1)were detected by quantitative real-time polymerase chain reaction or western blot,respectively.The secretions of inflammatory factors interleukins(IL)-6,IL-8 and tumor necrosis factor-?(TNF-?)were detected by ELISA assay.Western blot assay was used to analyze the expression levels of E-cadherin,vimentin,?-smooth muscle actin(?-SMA),ERK1/2,STAT3,p-ERK1/2 and p-STAT3 protein.The interaction between Let-7c-5p and RAC 1 was confirmed by bioinformatics analysis and Dual-luciferase reporter assay.ResultLet-7c-5p was down-regulated in COPD tissues and cigarette smoke extract(CSE)-induced 16HBE cells.Functional experiment indicated overexpressed Let-7c-5p blocked CSE-induced inflammation,epithelial mesenchymal transition(EMT)and ERK1/2 and STAT3 activation in 16HBE cells,reflected by suppressing pre-inflammatory factors such as IL-6,IL-8 and TNF-? and the protein of Vimentin,?-SMA,p-ERK1/2 and p-STAT3.Moreover,RAC1 was confirmed to be target of Let-7c-5p.RAC1 was up-regulated and negatively regulated by Let-7c-5p in 16HBE cells.RAC1 could aggravate CSE-induced inflammation,EMT as well as ERK1/2 and STAT3 activation in 16HBE cells.In addition,rescue assay displayed that overexpressed Let-7c-5p exerted the inhibitory effect in CSE-induced 16HBE cells via targeting RAC 1.ConclusionLet-7c-5p protected against CSE-induced lung inflammation,EMT by targeting RAC1 in COPD,and these processes might act through the activation of ERK1/2 and STAT3 pathways,which providing a potential therapeutic target for CSE-induced COPD therapy.