Downregulation of microRNA‑423‑5p suppresses TGF‑β1‑induced EMT by targeting FOXP4 in airway fibrosis

Chen,Yi; Chen,Yi; Li,Xuan; Li,Xuan; Li,Yishi; Li,Yishi; Wu,Yongchang; Wu,Yongchang; Huang,Guichuan; Huang,Guichuan; Wang,Xin; Wang,Xin; Guo,Shuliang; Guo,Shuliang

doi:10.3892/mmr.2022.12758

Downregulation of microRNA‑423‑5p suppresses TGF‑β1‑induced EMT by targeting FOXP4 in airway fibrosis

Authors:
- Yi Chen
- Xuan Li
- Yishi Li
- Yongchang Wu
- Guichuan Huang
- Xin Wang
- Shuliang Guo
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Affiliations: Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Clinical Nutrition, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: May 31, 2022 https://doi.org/10.3892/mmr.2022.12758
Article Number: 242
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Airway fibrosis (AF) is a common disease that can severely affect patient prognosis. Epithelial‑mesenchymal transition (EMT) participates in the pathophysiological development of AF and several studies have demonstrated that some microRNAs (miRNAs) contribute to the development of EMT. The aim of this study was to investigate the function of miR‑423‑5p in the EMT process and its possible underlying mechanism in BEAS‑2B cells. The present study utilized the BEAS‑2B cell line to model EMT in AF. Online tools, fluorescence in situ hybridization analysis and an RNA pull‑down assay were used to identify potential target genes of miR‑423‑5p. In addition, immunohistochemistry, wound healing assays, Transwell migration assays, flow cytometry, enzyme‑linked immunosorbent assay, reverse transcription‑quantitative PCR, western blot analysis and immunofluorescence staining were used to determine the function of miR‑423‑5p and its target gene in the EMT process in AF. The results indicated that the miR‑423‑5p expression in AF tissues and BEAS‑2B cells stimulated with 10 ng/ml TGF‑β1 for 24 h was significantly increased compared with that in the control group. Overexpression of miR‑423‑5p facilitated TGF‑β1‑induced EMT in BEAS‑2B cells; by contrast, downregulation of miR‑423‑5p suppressed TGF‑β1‑induced EMT in BEAS‑2B cells. Furthermore, forkhead box p4 (FOXP4) was identified as a potential target gene of miR‑423‑5p and changes in the miR‑423‑5p and FOXP4 expression were shown to significantly affect the expression of PI3K/AKT/mTOR pathway members. In summary, overexpression of miR‑423‑5P promoted the EMT process in AF by downregulating FOXP4 expression and the underlying mechanism may partly involve activation of the PI3K/AKT/mTOR pathway.

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