Protective role of microRNA-454-3p in neonatal hypoxic-ischaemic encephalopathy by targeting ST18

Abstract

Hypoxic-ischaemic encephalopathy (HIE) resulting from perinatal asphyxia or intrapartum-related events is a common cause of neonatal brain damage death among neonatal brain injury and term infants. However, the potential mechanisms of brain injury in term infants with HIE remain to be elucidated. This study aimed to investigate the role of miR-454-3p in HIE. The protective effect of microRNA-454-3p (miR-454-3p) targeting ST18 on neonatal HIE was investigated by the HIE rat model and primary rat nerve cell oxygen and glucose deprivation (OGD) model. The expression of miR-454-3p was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Cell apoptosis and viability was detected by flow cytometry and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, respectively. TargetScan predicted the binding sites between miR-454-3p and ST18. Dual luciferase reporter system was used to validate the relationship between ST18 and miR-454-3p. We found a significant decrease in miR-454-3p expression in the brain tissue of rats with HIE, while apoptosis and S100B and neuron-specific enolase (NSE) expression were significantly increased. In addition, miR-454-3p was significantly decreased in OGD-induced neurons, while the mRNA and protein expression of ST18 was significantly increased. OGD reduced neuronal cell viability and increased cell apoptosis were significantly inhibited by miR-454-3p mimic, but all these effects were significantly reversed by over-expression of ST18 gene. In conclusion, our study suggested that miR-454-3p was down-regulated in HIE rats, and it could attenuate OGD-induced neuronal apoptosis by targeting ST18, thereby playing a protective role in HIE, which might become a new and effective therapeutic target for HIE.