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