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The following is a summary of “Causal role of MiRNAs in chronic rhinosinusitis: mendelian randomization and validation study,” published in the April 2025 issue of Allergy, Asthma & Clinical Immunology by Shi et al. 

The epigenetic landscape of chronic rhinosinusitis (CRS) has advanced, but the causal microRNAs (miRNAs) in its pathogenesis remain undefined. 

Researchers conducted a retrospective study to identify miRNAs causally involved in CRS and explore their clinical relevance. The study also aimed to uncover the molecular mechanisms underlying their effects. 

They employed mendelian randomization (MR) analysis using mirQTLs as exposure variables and 2 independent CRS datasets as outcomes to identify miRNAs causally linked to CRS. Sensitivity analyses ensured the robustness of the findings. Expression levels of identified CRS-associated miRNAs were validated using qRT-PCR, and diagnostic potential was assessed through ROC curve analysis. Target genes and pathways regulated by the causal miRNAs were predicted via MiRNet and enrichment analyses, followed by experimental validation using western blotting and immunohistochemistry. 

The results showed that MiR-130a-3p and miR-196b-5p were significantly associated with an increased risk of CRS, while miR-339-3p was linked to a decreased risk. These associations were confirmed by qRT-PCR, with no evidence of pleiotropy or heterogeneity. ROC analysis demonstrated diagnostic potential for these miRNAs. Enrichment and experimental analyses indicated activation of the MAPK and PI3K-AKT pathways by target genes of the positively and negatively associated miRNAs, respectively. 

Investigators found that MiR-130a-3p and miR-196b-5p were positively associated with CRS risk, while miR-339-3p was protective. The MAPK and PI3K-AKT pathways likely mediated the effects of these causal miRNAs, providing insight into the molecular mechanisms of CRS. 

Source: aacijournal.biomedcentral.com/articles/10.1186/s13223-025-00957-4