miR-200a-3p regulates epithelial-mesenchymal transition and inflammation in chronic rhinosinusitis with nasal polyps by targeting ZEB1 via ERK/p38 pathway

BackgroundSeveral biological processes are regulated by miR-200a-3p, including cell proliferation, migration, and epithelial-mesenchymal transition (EMT). In this study we aimed to uncover the diagnostic value and molecular mechanisms of miR-200a-3p in chronic rhinosinusitis with nasal polyps (CRSwNP). MethodsThe expressions of miR-200a-3p were detected by quantitative real-time polymerase chain reaction (qRT-PCR), Zinc finger E-box binding homeobox 1 (ZEB1) levels were examined by qRT-PCR and immunofluorescence staining. The interaction between miR-200a-3p and ZEB1 was predicted by TargetScan Human 8.0 and confirmed by dual-luciferase reporter assays. In addition, the effect of miR-200a-3p and ZEB1 on EMT-related makers and inflammation cytokines was assessed by qRT-PCR and Western blotting in human nasal epithelial cells (hNEpCs) and primary human nasal mucosal epithelial cells (hNECs). ResultsWe found that miR-200a-3p was downregulated in non-eosinophilic and eosinophilic CRSwNP patients when compared with controls. The diagnostic value of miR-200a-3p in serum is reflected by the receiver operating characteristic curve and the 22-item Sino-Nasal Outcome Test. Bioinformatic analysis and luciferase reporter assay identified ZEB1 as a target of miR-200a-3p. ZEB1 was more highly expressed in CRSwNP than in controls. Furthermore, miR-200a-3p inhibitor or ZEB1 overexpression significantly suppressed the epithelial marker E-cadherin; promoted the activation of vimentin, & alpha;-spinal muscle atrophy, and N-cadherin; and aggravated inflammation in hNEpCs. Knockdown of ZEB1 significantly alleviated the cellular remodeling caused by miR-200a-3p inhibitor via the extracellular signal-regulated kinase (ERK)/p38 pathway in hNECs. ConclusionsmiR-200a-3p suppresses EMT and inflammation by regulating the expression of ZEB1 via the ERK/p38 pathway. Our study presents new ideas for protecting nasal epithelial cells from tissue remodeling and finding a possible target for disease.