Abstract
PURPOSE: Despite significant advancements in the epigenetics of chronic rhinosinusitis (CRS), particularly in the domain of microRNA (miRNA), little is known about miRNAs that play a causal role in CRS. This study aims to identify miRNAs with a causal relationship to CRS and explore their potential clinical value and mechanisms in CRS. METHODS: We conducted small RNA sequencing on blood and nasal samples to find miRNAs with consistent expression differences in CRS. These miRNAs were confirmed via qRT-PCR and assessed for clinical relevance through Spearman correlation and statistical analysis used to evaluate diagnostic accuracy. Bidirectional Mendelian randomization (MR, a genetic causal inference method) analyzed their causal links to CRS. Target genes of causally significant miRNAs were identified using miRWalk, and their mechanisms were explored through pathway enrichment and validation studies. RESULTS: We identified differentially expressed miRNAs in blood and nasal tissues using a |log2(Fold Change)| > 0.58 and P-value < 0.05 threshold. Following False Discovery Rate correction, hsa-miR-941 was identified as an upregulated miRNA in both CRS patient samples. The experimental validation of miR-941 expression closely matched sequencing results. Spearman and statistical analysis associated miR-941 expression changes with CRS severity and diagnostic accuracy. Bidirectional MR demonstrated a significant association of miR-941 with CRS risk, without evidence of reverse causality. Target gene and Western blot assays suggested miR-941's potential influence on CRS through the PI3K/AKT pathway. CONCLUSION: There is a positive causal relationship between hsa-miR-941 and CRS, making hsa-miR-941 a valuable target for the diagnosis and treatment of CRS. These findings position miR-941 as a valuable biomarker and therapeutic target, providing new opportunities for precision medicine in CRS treatment. miR-941 may exert its effects by modulating the PI3K/AKT signaling pathway.