miR‑106b‑5p targeting SIX1 inhibits TGF‑β1‑induced pulmonary fibrosis and epithelial‑mesenchymal transition in asthma through regulation of E2F1

Liu,Shuang; Chen,Xi; Zhang,Siqing; Wang,Xinyu; Du,Xiaoliu; Chen,Jiahe; Zhou,Guoping

doi:10.3892/ijmm.2021.4857

miR‑106b‑5p targeting SIX1 inhibits TGF‑β1‑induced pulmonary fibrosis and epithelial‑mesenchymal transition in asthma through regulation of E2F1

Authors:
- Shuang Liu
- Xi Chen
- Siqing Zhang
- Xinyu Wang
- Xiaoliu Du
- Jiahe Chen
- Guoping Zhou
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Affiliations: Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Respiratory Medicine, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: January 19, 2021 https://doi.org/10.3892/ijmm.2021.4857
Article Number: 24
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Asthma is an inflammatory disease of the airways, characterized by lung eosinophilia, mucus hypersecretion by goblet cells and airway hyper‑responsiveness to inhaled allergens. The present study aimed to identify the function of microRNA (miR/miRNA)‑106b‑5p in TGF‑β1‑induced pulmonary fibrosis and epithelial‑mesenchymal transition (EMT) via targeting sine oculis homeobox homolog 1 (SIX1) through regulation of E2F transcription factor 1 (E2F1) in asthma. Asthmatic mouse models were induced with ovalbumin. miRNA expression was evaluated using reverse transcription‑quantitative PCR. Transfection experiments using bronchial epithelial cells were performed to determine the target genes. A luciferase reporter assay system was applied to identify the target gene of miR‑106b‑5p. The present study revealed downregulated miR‑106b‑5p expression and upregulated SIX1 expression in asthmatic mice and TGF‑β1‑induced BEAS‑2B cells. Moreover, miR‑106b‑5p overexpression inhibited TGF‑β1‑induced fibrosis and EMT in BEAS‑2B cells, while miR‑106b‑5p‑knockdown produced the opposite effects. Subsequently, miR‑106b‑5p was found to regulate SIX1 through indirect regulation of E2F1. Additionally, E2F1‑ and SIX1‑knockdown blocked TGF‑β1‑induced fibrosis and EMT in BEAS‑2B cells. In addition, miR‑106b‑5p negatively regulated SIX1 via E2F1 in BEAS‑2B cells. The present study demonstrated that the miR‑106b‑5p/E2F1/SIX1 signaling pathway may provide potential therapeutic targets for asthma.

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