Downregulation of microRNA-423-5p suppresses TGF-beta 1-induced EMT by targeting FOXP4 in airway fibrosis

作者全名："Chen, Yi; Li, Xuan; Li, Yishi; Wu, Yongchang; Huang, Guichuan; Wang, Xin; Guo, Shuliang"

作者地址："[Chen, Yi; Li, Yishi; Wu, Yongchang; Huang, Guichuan; Wang, Xin; Guo, Shuliang] Chongqing Med Univ, Dept Pulm & Crit Care Med, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China; [Li, Xuan] Chongqing Med Univ, Dept Clin Nutr, Affiliated Hosp 1, Chongqing 400016, Peoples R China"

通信作者："Guo, SL (通讯作者)，Chongqing Med Univ, Dept Pulm & Crit Care Med, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China."

来源：MOLECULAR MEDICINE REPORTS

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000811681000001

JCR分区：Q3

影响因子：3.4

年份：2022

卷号：26

期号：1

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结束页：　

文献类型：Article

关键词：microRNA-423-5p; airway fibrosis; forkhead box p4; epithelial-mesenchymal transition; PI3K; AKT; mTOR signaling pathway

摘要："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-beta 1 for 24 h was significantly increased compared with that in the control group. Overexpression of miR-423-5p facilitated TGF-beta 1-induced EMT in BEAS-2B cells; by contrast, downregulation of miR-423-5p suppressed TGF-beta 1-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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