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Combinatorial Chemistry & High Throughput Screening

Author(s): Chunlei Zhang, Xiuting Li, Na Liu, Zijian Feng and Chengyuan Zhang*

DOI: 10.2174/1386207323666201211091312

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MicroRNA-96 is Downregulated in Sepsis Neonates and Attenuates LPSInduced Inflammatory Response by Inhibiting IL-16 in Monocytes

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Abstract

Background: Neonatal sepsis (NS) remains one of the leading causes of mortality among newborns. This study found the deregulated microRNA-96 (miR-96) in NS neonates, and aimed to evaluate the clinical significance of miR-96, as well as its effect on LPS-induced inflammatory response in monocytes. In addition, the relationship of interleukin-16 (IL-16) and miR-96 was investigated to understand the underlying mechanisms.

Methods: Expression of miR-96 was examined using real-time quantitative PCR. Monocytes stimulated by LPS was used to mimic excessive inflammation in the pathogenesis of NS. The enzyme-linked immunosorbent assay was applied to evaluate pro-inflammatory cytokine levels. A luciferase reporter assay was used to confirm the interaction between miR-96 and IL-16.

Results: Serum miR-96 expression was decreased in NS newborns and had considerable diagnostic value for NS screening. LPS inhibited miR-96 expression in monocytes, and the overexpression of miR-96 could reverse the effects of LPS on the inflammation of monocytes. IL-16 was a target gene of miR-96 and negatively correlated with miR-96 levels in NS neonates. The inhibited inflammatory responses induced by miR-96 overexpression was abolished by the elevated IL-16 in monocytes.

Conclusion: All the data reveal that serum decreased miR-96 may serve as a candidate noninvasive biomarker for NS diagnosis. In addition, miR-96 inhibits LPS-induced inflammatory responses by targeting IL-16 in monocytes. The miR-96/IL-16 axis may provide novel therapeutic targets for NS treatment.

Keywords: MicroRNA-96, neonatal sepsis, diagnosis, inflammation, monocyte, interleukin-16.

Graphical Abstract

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