STAT1 mediates the PI3K/AKT pathway through promoting microRNA-18a in nasal polyps

Epithelial to mesenchymal transition (EMT) is linked to the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP). The involvement of STAT1 has been reported in CRSwNP. However, its specific role in regulating EMT in CRSwNP is not clear. We sought to evaluate the role of STAT1 in EMT in CRSwNP using clinical samples and a murine model.

Comprehensive analysis of differentially expressed genes was performed in nasal polyps from the CRSwNP patients, followed by pathway enrichment analysis. After bioinformatics prediction, the relationships between microRNA-18a (miR-18a) and PTEN or STAT1 were examined using dual-luciferase and RIP assays, respectively. The expression of STAT1, PTEN, and miR-18a in nasal tissues was detected using RT-qPCR, immunohistochemistry, and in situ hybridization. After the alteration of gene expression in mice with CRSwNP, western blot, RT-qPCR, and HE staining were conducted to detect EMT-related proteins, inflammatory factor secretion, inflammatory cell infiltration, and the PI3K/AKT pathway activity in nasal tissues.

STAT1 and miR-18a were highly expressed, and PTEN was poorly expressed in the nasal polyp. STAT1 promoted transcription of miR-18a, which targeted PTEN. Downregulation of STAT1 and miR-18a inhibited the EMT and inflammatory cell infiltration, while depletion of PTEN promoted the EMT and inflammatory cell infiltration in the nasal polyp. The PI3K/AKT pathway was activated in the nasal polyp and regulated by the STAT1/miR-18a/PTEN axis.

STAT1 acts as a transcription factor to promote transcription of miR-18a, and miR-18a targets PTEN to exacerbate the inflammatory response and EMT in CRSwNP.