miR-146a-5p alleviates sepsis-induced acute lung injury by targeting the IRAK1/TRAF6/NF-κB signaling pathway

Sepsis-Acute Lung Injury (S-ALI) is characterized by an excessive inflammatory response and has a high mortality rate. The regulatory role of microRNAs (miRNAs) remains to be further explored. Including S-ALI patients and healthy individuals, combined with cell models, through techniques such as qRT-PCR, dual luciferase reporter assay, and multivariate Logistic regression, the expression and correlation of miR-146a-5p, IRAK1, and pro-inflammatory factors were analyzed to clarify the regulatory mechanism. In patients with S-ALI, the expression of miR-146a-5p was significantly decreased, while the expressions of IRAK1 and pro-inflammatory factors were significantly increased. Cell experiments confirmed that miR-146a-5p directly targeted IRAK1. Western blot further demonstrated that miR-146a-5p suppressed the IRAK1/TRAF6/NF-κB signaling cascade, thereby reducing pro-inflammatory factor production. Multivariate logistic regression analysis identified plasma miR-146a-5p as an independent discriminating factor for S-ALI versus healthy subjects. ROC analysis revealed its favourable diagnostic performance to distinguish S-ALI patients from healthy controls. miR-146a-5p inhibits the inflammatory response in S-ALI by targeting the IRAK1/TRAF6/NF-κB pathway. These results highlight miR-146a-5p as a candidate molecule deserving further investigation in S-ALI. Not applicable.