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Deregulated miR-384 serves as a biomarker in neonatal hypoxic-ischemic encephalopathy and alleviates microglia-mediated neuroinflammation

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Abstract

Microglia-mediated neuroinflammation is important in the pathogenesis of neonatal hypoxic-ischemic encephalopathy (HIE). This study aimed to investigate the expression of microRNA-384 (miR-384) in HIE newborns and evaluate the clinical and functional role of miR-384 in HIE diagnosis and neuroinflammation. The expression of miR-384 was estimated using quantitative real-time PCR. The levels of proinflammatory cytokines were examined using ELISA. Receiver operating characteristic (ROC) analysis was applied to evaluate the diagnostic performance of miR-384. The oxygen–glucose deprivation (OGD) experiment was adopted to activate primary neonatal microglia. A putative target of miR-384 was analyzed by bioinformatics prediction and a luciferase reporter assay. The expression of miR-384 was decreased in the serum of HIE newborns and OGD-induced activated microglia. Serum miR-384 had relatively high diagnostic accuracy for the screening of HIE cases from healthy newborns and the differentiation between newborns with different HIE severities. The OGD-induced increase in microglial neuroinflammation was significantly attenuated by the overexpression of miR-384, and AKT3, as a downstream target of miR-384, was inhibited by miR-384 in activated microglia. The data of this study demonstrated that decreased serum miR-384 expression may be a novel noninvasive biomarker for the diagnosis and progression of neonatal HIE. miR-384 can inhibit the neuroinflammation in activated microglia, which may be mediated by targeting AKT3.

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Data availability

All data analyzed in this study are included in the manuscript.

Abbreviations

HIE:

Hypoxic-ischemic encephalopathy

miR-384:

MicroRNA-384

ROC:

Receiver operating characteristic

OGD:

Oxygen–glucose deprivation

CSF:

Cerebrospinal fluid

miRNAs:

MicroRNAs

3′-UTR:

3′-Untranlated region

ELISA:

Enzyme-linked immunosorbent assay

AKT3:

V-akt murine thymoma viral oncogene homolog 3

WT:

Wild type

MUT:

Mutant type

ROC:

Receiver operating characteristic

AUC:

Area under the curve

qRT-PCR:

Quantitative real-time PCR

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Authors and Affiliations

Authors

Contributions

GZ and ML designed the study, analyzed the clinical and cell experiments data and wrote the manuscript. MY collected the clinical data of the infants and constructed the cell experiment model.

Corresponding author

Correspondence to Min Li.

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Conflict of interest

The authors declare that they have no competing interests.

Ethics approval

The experiments in this study were approved by the Ethics Committee of Maternal and Child Health Hospital of Linyi.

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A written informed consent was obtained from each infant’s parents.

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The consent for publication was obtained.

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Zhang, G., Ye, M. & Li, M. Deregulated miR-384 serves as a biomarker in neonatal hypoxic-ischemic encephalopathy and alleviates microglia-mediated neuroinflammation. Mol Biol Rep 47, 5411–5420 (2020). https://doi.org/10.1007/s11033-020-05631-z

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  • DOI: https://doi.org/10.1007/s11033-020-05631-z

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