Clinical significance of miR‑181a in patients with neonatal sepsis and its regulatory role in the lipopolysaccharide‑induced inflammatory response

Liu,Guozhi; Liu,Wei; Guo,Jie

doi:10.3892/etm.2020.8408

Clinical significance of miR‑181a in patients with neonatal sepsis and its regulatory role in the lipopolysaccharide‑induced inflammatory response

Authors:
- Guozhi Liu
- Wei Liu
- Jie Guo
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Affiliations: Department of Neonatology, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China
Published online on: January 2, 2020 https://doi.org/10.3892/etm.2020.8408
Pages: 1977-1983

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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.

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