Abstract
PURPOSE: Eosinophilic chronic rhinosinusitis (ECRS) is characterized by severe symptoms and a high recurrence rate, yet its pathogenesis remains unclear and difficult to manage with current treatments. This study aims to investigate the role of circRNA_0021727 in ECRS-related inflammation, as well as the regulatory interactions among circRNA_0021727, miRNA_145_5p, and ADAM12 in ECRS. METHODS: Primary nasal epithelial cells (PNECs) were isolated from nasal polyp tissues of 10 ECRS patients and inferior turbinate tissues of 10 nasal septum deviation patients for differential expression analysis. Primary cell cultures were established for overexpression and knockdown of circRNA_0021727 and miRNA_145_5p, which were generated to assess ADAM12 expression. An inflammatory model was induced using IL-13 treatment, and the expression levels of GM-CSF, EOTAXIN, and MUC5AC were measured. RESULTS: In ECRS epithelium, circRNA_0021727 and ADAM12 were upregulated, whereas miRNA_145_5p was downregulated. Overexpression of circRNA_0021727 led to decreased miRNA-145-5p and increased ADAM12 expression, whereas knockdown of circRNA_0021727 had the opposite effect. Similarly, overexpression of miRNA_145_5p resulted in decreased ADAM12 levels, while its knockdown increased ADAM12 expression. After IL-13 treatment, GM-CSF, EOTAXIN, and MUC5AC expression levels were elevated in circRNA_0021727-overexpressing cells and reduced in knockdown cells. Conversely, miRNA_145_5p overexpression decreased these inflammatory markers, while knockdown increased their levels. CONCLUSION: The circRNA_0021727-miRNA-145-5p-ADAM12 regulatory axis plays a role in ECRS pathogenesis. circRNA_0021727 promotes ECRS-related inflammation, suggesting its potential as a therapeutic target for managing the disease.