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

Abstract Background Several 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). Methods The 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). Results We 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, α‐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. Conclusions miR‐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.