Down-Regulated microRNA-192-5p Protects Against Hypoxic-Ischemic Brain Damage via Regulation of YAP1-Mediated Hippo Signaling Pathway.

Abstract

Hypoxic-ischemic brain damage (HIBD) is a familiar neurological disorder. Emerging reports manifest that microRNAs (miRs) are related to the progression of HIBD. The goal of this study is to explore the mechanism of miR-192-5p in HIBD via regulation of Yes-associated protein 1 (YAP1)-mediated Hippo signaling pathway. The miR-192-5p, YAP1, and Hippo pathway-related factors Phospho (p)-Triaminoguanidinium azide (TAZ) in hippocampal tissues and neurons were detected. The regulatory relationship between miR-192-5p and YAP1 was verified. Neonatal hypoxic ischemia and oxygen-glucose deprivation (OGD) were used to simulate HIBD in vivo and in vitro. The neurobehavioral impairment, neuronal damage and vascular endothelial growth factor (VEGF) expression of neonatal rats in each group were detected. The viability, apoptosis and VEGF expression of hippocampal neurons in each group were also examined. MiR-192-5p expression was elevated while YAP1 expression was reduced in hippocampal tissues of HIBD rats in vivo and OGD neurons in vitro. MiR-192-5p had a targeting relation with YAP1. Suppressed miR-192-5p or overexpressed YAP1 in HIBD rats alleviated neurobehavioral impairment and neuronal damage, and decreased the expression levels of p-TAZ and VEGF expression in vivo. Reduced miR-192-5p or augmented YAP1 decelerated the neuron apoptosis, decreased the p-TAZ level and VEGF level and promoted cell viability of OGD hippocampal neurons in vitro. The study highlights that inhibited miR-192-5p protects against HIBD via regulation of YAP1 and Hippo signaling pathway, which is beneficial for HIBD treatment.