WTAP Advances Epithelial‐Mesenchymal Transition of Eosinophilic Chronic Rhinosinusitis With Nasal Polyps by Increasing IRF9 N6‐Methyladenosine Modifications

N6‐methyladenosine (m6A) represents the most prevalent RNA epigenetic modification in eukaryotic cells. However, its role in eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains poorly characterized. This study aimed to elucidate the mechanism by which m6A modification contributes to epithelial‐mesenchymal transition (EMT) in ECRSwNP. A stable IFN‐β‐induced human nasal epithelial cell (HNEpC) model was established to induce EMT. The expression of Wilms' tumour 1‐associated protein (WTAP) and the total m6A/A ratio were assessed in HNEpCs. Subsequently, methylated RNA immunoprecipitation sequencing (MeRIP‐seq) was performed to identify potential targets of WTAP. The specific interaction between WTAP and its presumed target was confirmed through RNA immunoprecipitation assays and RNA pull‐down experiments. Additionally, rescue experiments and MeRIP were conducted to elucidate the underlying mechanism. A murine model of ECRSwNP was employed to further demonstrate WTAP's role in mediating EMT in ECRSwNP. Our findings demonstrate that WTAP plays a significant role in IFN‐β‐induced inflammation of nasal epithelial cells. WTAP upregulation correlated with inflammation and EMT in ECRSwNP. Functionally, WTAP knockdown reduced the expression of EMT biomarkers in HNEpCs. Mechanistically, MeRIP‐seq identified IRF9 as a downstream target of WTAP. WTAP knockdown significantly reduced m6A modification levels on IRF9 mRNA, leading to decreased IRF9 expression. Furthermore, m6A‐methylated IRF9, mediated by WTAP, was recognized by the m6A reader protein YTHDF1, which promoted IRF9 mRNA translation and stability. Finally, decreased WTAP expression significantly inhibited inflammation and EMT in the ECRSwNP mouse model. Our findings underscore the functional role of WTAP in ECRSwNP. WTAP promotes IRF9 mRNA translation through YTHDF1 recognition, thereby facilitating α‐SMA and vimentin transcription while promoting E‐cadherin and β‐catenin degradation in both HNEpCs and the ECRSwNP mouse model.