MicroRNA-145-5p Regulates the Epithelial-Mesenchymal Transition in Nasal Polyps by Targeting Smad3
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Objectives. The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposesa substantial burden on both patients and society. The formation of nasal polyps in patients with CRS is closely relat-ed to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA)plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; how-ever, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear. Methods. The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerasechain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasalpolyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genesof miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evalu-ated using cell migration assay and wound healing assays. Results. miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. Invitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-β1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression. Conclusion. Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study pro-vide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.
Abstract
Objectives. The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposesa substantial burden on both patients and society. The formation of nasal polyps in patients with CRS is closely relat-ed to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA)plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; how-ever, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear. Methods. The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerasechain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasalpolyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genesof miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evalu-ated using cell migration assay and wound healing assays. Results. miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. Invitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-β1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression. Conclusion. Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study pro-vide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.
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