The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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MicroRNA-21 promotes epithelial-mesenchymal transition and migration of human bronchial epithelial cells by targeting poly (ADP-ribose) polymerase-1 and activating PI3K/AKT signaling

  • Zhang, Shiqing (Department of The Second Clinical College, Dalian Medical University) ;
  • Sun, Peng (Department of Respiratory and Critical Care Medicine, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University) ;
  • Xiao, Xinru (Department of The Second Clinical College, Dalian Medical University) ;
  • Hu, Yujie (Department of The Second Clinical College, Dalian Medical University) ;
  • Qian, Yan (Department of Respiratory and Critical Care Medicine, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University) ;
  • Zhang, Qian (Department of Respiratory and Critical Care Medicine, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University)
  • Received : 2021.11.26
  • Accepted : 2022.03.05
  • Published : 2022.07.01
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Abstract

Epithelial-mesenchymal transition (EMT) is known to be involved in airway remodeling and fibrosis of bronchial asthma. However, the molecular mechanisms leading to EMT have yet to be fully clarified. The current study was designed to reveal the potential mechanism of microRNA-21 (miR-21) and poly (ADP-ribose) polymerase-1 (PARP-1) affecting EMT through the PI3K/AKT signaling pathway. Human bronchial epithelial cells (16HBE cells) were transfected with miR-21 mimics/inhibitors and PARP-1 plasmid/small interfering RNA (siRNA). A dual luciferase reporter assay and biotin-labeled RNA pull-down experiments were conducted to verify the targeting relationship between miR-21 mimics and PARP-1. The migration ability of 16HBE cells was evaluated by Transwell assay. Quantitative real-time polymerase chain reaction and Western blotting experiments were applied to determine the expression of Snail, ZEB1, E-cadherin, N-cadherin, Vimentin, and PARP-1. The effects of the PI3K inhibitor LY294002 on the migration of 16HBE cells and EMT were investigated. Overexpression of miR-21 mimics induced migration and EMT of 16HBE cells, which was significantly inhibited by overexpression of PARP-1. Our findings showed that PARP-1 was a direct target of miR-21, and that miR-21 targeted PARP-1 to promote migration and EMT of 16HBE cells through the PI3K/AKT signaling pathway. Using LY294002 to block PI3K/AKT signaling pathway resulted in a significant reduction in the migration and EMT of 16HBE cells. These results suggest that miR-21 promotes EMT and migration of HBE cells by targeting PARP-1. Additionally, the PI3K/AKT signaling pathway might be involved in this mechanism, which could indicate its usefulness as a therapeutic target for asthma.

Keywords

Acknowledgement

This study was supported by grants from the Jiangsu province social development project (BE2020651 to Q.Z.), and in part from the Jiangsu province "333 talents" project (BRA2020015 to Q.Z.), the Changzhou Sci & Tech Program (CE20205023 to Q.Z.).

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