Abstract
Neonatal sepsis (NS) poses a serious threat to the health of neonates worldwide. The present study aimed to investigate the diagnostic value of microRNA (miR)-181a in patients with NS and the regulatory role of miR-181a in lipopolysaccharide (LPS)-induced inflammation. A total of 102 neonates with NS and 50 neonates without sepsis were enrolled in the present study. The serum levels of miR-181a were estimated using reverse transcription-quantitative PCR. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic value of miR-181a for NS. The effect of miR-181a on the expression of Toll-like receptor (TLR)4 was assessed after modification of the expression of miR-181a in monocytes isolated from the blood of neonates in vitro. An ELISA was used to measure the concentration of inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-8 in the supernatant of monocytes. The serum levels of miR-181a were decreased in patients with NS compared with those in the controls. The area under the ROC curve of miR-181a was 0.893 with a sensitivity of 83.3% and a specificity of 84.0%. LPS stimulation in monocytes also led to a decrease in the expression of miR-181a. TLR4 was proven to be a direct target gene of miR-181a, according to the results of a luciferase reporter assay, and overexpression of miR-181a suppressed TLR4 expression in monocytes. Regarding LPS-induced inflammation, it was revealed that the upregulated levels of TNF-α and IL-8 induced by LPS were reduced by overexpression of miR-181a in monocytes. In conclusion, decreased serum levels of miR-181a may serve as a diagnostic biomarker in patients with NS and overexpression of miR-181a inhibits the LPS-induced inflammatory response at least partially by targeting TLR4. Aberrant miR-181a may be a non-invasive biomarker for NS patients, and provide a novel insight into the pathologic mechanisms of action behind the development of NS.