Multi-Omics and Molecular Dynamics Analysis for Biomarker Discovery in Chronic Rhinosinusitis With Nasal Polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifaceted inflammatory condition that significantly affects patients clinically. It is vital to comprehend the basic molecular mechanisms and to discover new biomarkers. This research combines multi-omics data, molecular docking, and dynamic simulations to investigate gene functions and possible biomarkers related to CRSwNP. Initially, we discovered 555 differentially expressed genes (DEGs) induced by alpha-toxin (Hla) and 8119 DEGs associated with CRSwNP obtained from the Gene Expression Omnibus (GEO) database. Utilizing GO/KEGG enrichment analysis, we identified the NF-κB signaling pathway as significant. We identified 16 genes associated with TGF-β receptor signaling in epithelial-mesenchymal transition (EMT) through PathCards and subsequently intersected these with the differentially expressed genes from two datasets. This analysis revealed the presence of one gene, PRKCZ. Additionally, single-cell sequencing offered deeper insights into cellular diversity, elucidating the expression patterns of PRKCZ across various cell types. Molecular docking and dynamics simulations established that the proteasome inhibitor MG132 can create a stable complex with PRKCZ. In conclusion, qRT-PCR, Western blot, immunohistochemistry, and fluorescence assays validated that Hla stimulation markedly heightened the levels of inflammatory pathway markers in human nasal mucosal epithelial cells. Importantly, the inhibition of PRKCZ by MG132 resulted in a significant reduction of these marker expression levels, offering a foundation for targeted therapeutic interventions. The current research demonstrates that alpha-toxin from Staphylococcus aureus promotes EMT in CRSwNP via the NF-κB/TGF-β signaling axis. A significant gene that may serve as a potential therapeutic target is PRKCZ.