miR‑320a‑3P alleviates the epithelial‑mesenchymal transition of A549 cells by activation of STAT3/SMAD3 signaling in a pulmonary fibrosis model

Wang,Xin; Wang,Jing; Huang,Guichuan; Li,Yishi; Guo,Shuliang

doi:10.3892/mmr.2021.11996

miR‑320a‑3P alleviates the epithelial‑mesenchymal transition of A549 cells by activation of STAT3/SMAD3 signaling in a pulmonary fibrosis model

Authors:
- Xin Wang
- Jing Wang
- Guichuan Huang
- Yishi Li
- Shuliang Guo
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Affiliations: Department of Respiratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Pharmacy, People's Hospital of Deyang City, Deyang, Sichuan 618000, P.R. China
Published online on: March 12, 2021 https://doi.org/10.3892/mmr.2021.11996
Article Number: 357
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pulmonary fibrosis (PF) is a common, chronic and incurable lung disease, in which the lungs become scarred over time. MicroRNAs (miRNAs/miRs) serve key roles in various biological processes, including cell proliferation, differentiation, apoptosis and the regulation of epithelial‑mesenchymal transition (EMT) process. The aim of the present study was to investigate the underlying mechanism of miR‑320a‑3p as a potential therapeutic target for PF. Clinical samples and microarray datasets collected from various databases were used to evaluate the expression of miR‑320a‑3p in PF. A549 cells were used to construct an EMT model of PF. A dual‑luciferase reporter assay system was used to identify target genes of miR‑320a‑3p. Western blot analysis and immunofluorescence staining were used to determine the roles of miR‑320a‑3p and its target genes in the EMT process in PF. The present study found that, compared with lung tissue of healthy control subjects, the expression of miR‑320a‑3p in lung tissue of PF patients was significantly reduced. The expression levels of miR‑320a‑3p decreased in TGF‑β1‑stimulated A549 cells in a time‑ and concentration‑dependent manner. The overexpression of miR‑320a‑3p suppressed EMT markers induced by TGF‑β1 in A549 cells and STAT3 was identified as a potential target gene of miR‑320a‑3p. Furthermore, the expression changes of miR‑320a‑3p and STAT3 were found to significantly affect the expression of phosphorylated SMAD3 in TGF‑β1‑stimulated A549 cells. Briefly, overexpression of miR‑320a‑3p could inhibit the EMT process in PF by downregulating STAT3 expression. The mechanism mediating these effects may partly involve crosstalk between the SMAD3 and STAT3.

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