miR-217 represses TGF-β1-induced airway smooth muscle cell proliferation and migration through targeting ZEB1

Publication date: December 2018Source: Biomedicine & Pharmacotherapy, Volume 108Author(s): Ying Gao, Botao Wang, Huanan Luo, Qing Zhang, Min XuAbstractAberrant proliferation and migration of airway smooth muscle cells (ASMCs) contribute to the pathogenesis of airway remodeling during asthma development. Here, the potential function of microRNA-217 (miR-217) on the cell proliferation and migration of TGF-β1-induced ASMCs and the involved mechanisms were investigated in this study. We found that miR-217 expression was apparently downregulated in a time and dose dependent characteristic in ASMCs exposed to transforming growth factor-β (TGF-β1) stimulation. Overexpression of miR-217 significantly inhibited TGF-β1-induced proliferation, migration, extracellular matrix (ECM) deposition, but promoted apoptosis in ASMCs, whereas, miR-217 inhibitor showed an opposed effect. Bioinformatics analyses revealed that the 3’-untranslated region (UTR) of ZEB1 was a potential target for miR-217, which was further confirmed by luciferase activity, qRT-PCR and western blot assay. In addition, rescue experiment also displayed that restoration of ZEB1 expression partially abrogated the inhibitory effect of miR-217 on TGF-β1-induced proliferation and migration in ASMCs. By chromatin immunoprecipitation (ChIP) assay, we further confirmed that the binding of ZEB1 to the fibronectin promoter in TGF-β1-treated ASMCs was reduced by miR-217 overexpression. Therefore, our findings suggested the po...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research