Role of miR-9 in Modulating NF-κB Signaling and Cytokine Expression in COVID-19 Patients

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has had a significant impact on global health, with severe cases often characterized by a worsening cytokine storm. Since it has been described that the NF-kappa B signaling pathway, regulated by microRNAs, could play a pivotal role in the inflammatory response, in this study, the role of miR-9 in modulating NF-kappa B signaling and inflammatory cytokine expression in COVID-19 patients was investigated. This observational retrospective single-center study included 41 COVID-19 patients and 20 healthy controls. Serum samples were analyzed for miR-9, NF-kappa B, and I kappa B alpha expression levels using RT-PCR. The expression levels and production of pro-inflammatory cytokines IL-6, IL-1 beta, and TNF-alpha were measured using RT-PCR and ELISA. Statistical analyses, including correlation and regression, were conducted to explore relationships between these variables. COVID-19 patients, particularly non-survivors, exhibited significantly higher miR-9 and NF-kappa B levels compared to controls. A strong positive correlation was found between miR-9 and NF-kappa B expression (r = 0.813, p < 0.001). NF-kappa B levels were significantly correlated with IL-6 (r = 0.971, p < 0.001), IL-1 beta (r = 0.968, p < 0.001), and TNF-alpha (r = 0.968, p < 0.001). Our findings indicate that miR-9 regulates NF-kappa B signaling and inflammation in COVID-19. Elevated miR-9 levels in non-survivors suggest its potential as a severity biomarker. While COVID-19 cases have decreased, targeting miR-9 and NF-kappa B could improve outcomes for other inflammatory conditions, including autoimmune diseases, highlighting the need for continued research in this area.