Let-7a inhibits proliferation and promotes apoptosis of human asthmatic airway smooth muscle cells.

The present study aimed to examine the changes of let-7a expression in asthmatic airway smooth muscle cells (ASMCs) and to analyze its effect on the proliferation and apoptosis of ASMCs, as well as the potential mechanism of action. Let-7a expression levels in ASMCs from asthmatic and non-asthmatic subjects were detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. Furthermore, let-7a mimics were transfected into ASMCs isolated from asthmatic patients, and the effect of let-7a on ASMC proliferation was examined using a Cell Counting Kit-8. In addition, the influence of let-7a on ASMC apoptosis was detected using flow cytometry and a caspase-3/7 activity assay. Target genes of let-7a were predicted using bioinformatics software, and the direct regulatory effect of let-7a on the potential target gene signal transducer and activator of transcription 3 (STAT3) was verified through a dual-luciferase reporter gene assay combined with RT-qPCR and western blot analysis. The results demonstrated that let-7a expression was significantly lower in ASMCs of asthmatic subjects compared with that in ASMCs of normal subjects. Furthermore, upregulation of let-7a expression in asthmatic ASMCs markedly inhibited cell proliferation and promoted cell apoptosis. The results of the dual-luciferase reporter gene assay indicated that let-7a selectively binds with the 3'-untranslated region of the STAT3 mRNA. In addition, let-7a mimics evidently reduced the mRNA and protein expression levels of STAT3 in asthmatic ASMCs. In conclusion, the present study demonstrates that let-7a expression is downregulated in ASMCs from asthmatic patients. Furthermore, let-7a suppresses the proliferation and promotes apoptosis of human asthmatic ASMCs, which may, at least partially, be associated with the downregulation of STAT3 expression.