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

Chen,Yan; Qiao,Lujun; Zhang,Zewen; Hu,Guoxin; Zhang,Jian; Li,Hongjia

doi:10.3892/etm.2019.7363

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

Authors:
- Yan Chen
- Lujun Qiao
- Zewen Zhang
- Guoxin Hu
- Jian Zhang
- Hongjia Li
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Affiliations: Department of Critical Care Medicine, Shengli Oilfield Center Hospital, Dongying, Shandong 257000, P.R. China, Department of Respiratory Disease, Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
Published online on: March 7, 2019 https://doi.org/10.3892/etm.2019.7363
Pages: 3327-3334
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 in vitro 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.

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