miR-186 Regulates Septic Hyperinflammation and Predicts Sepsis

Abstract

Sepsis is a life-threatening condition caused by infection-induced immune dysregulation. Clinically distinguishing sepsis from infection remains to be a challenge due to overlapping clinical features. Although miR-186 regulates cell proliferation and apoptosis, and was predicted to target immune-related genes, its role in sepsis is unclear. We retrospectively enrolled 21 infected patients and 20 sepsis patients. The miR-186 level in blood cells was detected using real-time PCR. Cytokine concentrations and lymphocyte subpopulation proportions were determined using flow cytometry. Clinical data were retrieved from medical records. The diagnostic ability of miR-186 was compared with procalcitonin and lactate using the receiver operating characteristic (ROC) curve. miR-186 was inhibited in human umbilical vein endothelial cells (HUVECs) and mice, followed by measurement of cytokine expression using real-time PCR and flow cytometry. The expression level of miR-186 was significantly higher in septic patients than in infected patients. miR-186 showed relatively better diagnostic performance for sepsis than procalcitonin and lactate. The in vitro assay showed that LPS enhanced miR-186 expression under a dose-dependent manner. In vitro miR-186 inhibition in HUVECs inhibited IL-1β, IL-6, and IL-8 expression. In vivo miR-186 inhibition significantly lowered IL-1β concentration and natural killer cell ratio. In this study, we found that miR-186 is significantly upregulated in sepsis and plays a regulatory role in cytokine expression, highlighting its potential as a diagnostic biomarker for sepsis.