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Original Article

Korean J Physiol Pharmacol 2022; 26(4): 239-253

Published online July 1, 2022 https://doi.org/10.4196/kjpp.2022.26.4.239

Copyright © Korean J Physiol Pharmacol.

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

Shiqing Zhang1,2, Peng Sun2, Xinru Xiao1,2, Yujie Hu1,2, Yan Qian2, and Qian Zhang2,*

1Department of The Second Clinical College, Dalian Medical University, Dalian 116000, China, 2Department of Respiratory and Critical Care Medicine, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou 213003, China

Correspondence to:Qian Zhang
E-mail: kezhang0601@163.com

Author contributions: S.Z. performed the protein electrophoresis test, Transwell assay and wrote the manuscript. P.S. and X.X. conducted part of the experiments. Y.H., Y.Q., and Q.Z. supervised and coordinated the study.

Received: November 26, 2021; Revised: March 3, 2022; Accepted: March 5, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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: Asthma, Epithelial-mesenchymal transition, MicroRNAs, PI3K/AKT signaling pathway, Poly (ADP-ribose) polymerase-1