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

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.