H19/miR-130a-3p/DAPK1 axis regulates the pathophysiology of neonatal hypoxic-ischemia encephalopathy

• Published in: Neuroscience research Vol. 163; pp. 52 - 62
• Main Authors: Feng, Mei, Zhu, Xuefen, Zhuo, Chengjie
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.02.2021
• Subjects: Animals; Apoptosis; DAPK1; Death-Associated Protein Kinases - genetics; Glucose; H19; Infarction, Middle Cerebral Artery; Mice; MicroRNAs - genetics; miR-130a-3p; Neonatal hypoxic-ischemia encephalopathy; Up-Regulation; H19; miR-130a-3p; Neonatal hypoxic-ischemia encephalopathy; DAPK1
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2020.03.005

•DAPK1 was upregulated while miR-130a-3p was downregulated in HIE.•MiR-130a-3p impaired cell apoptosis, ROS production, cerebral injury by targeting DAPK1.•H19 competitively bound with miR-130a-3p to enhance DAPK1 expression.•H19/miR-130a-3p/DAPK1 axis regulated the pathophysiology of neonatal HIE. Perinatal hypoxic ischemia encephalopathy (HIE) is a serious disease occurring in neonate. Growing studies have already validated the pivotal function of microRNAs (miRNAs) in a variety of diseases. However, whether miR-130a-3p participated in neonatal HIE remains vague. In this study, we planned to explore the molecular mechanism of H19/miR-130a-3p/DAPK1 axis in HIE. We established a in vivo mice model induced by middle cerebral artery occlusion/reperfusion (MCAO/R) and in vitro models of SH-SY5Y and N2a cells following oxygen-glucose deprivation and reperfusion (OGD/R) treatment. DAPK1 is widely explored in multiple diseases and bioinformatic analysis indicated miR-130a-3p potentially targeted DAPK1. We found DAPK1 expression was upregulated while miR-130a-3p expression was downregulated in HIE, MCAO/R mice model and OGD/R treated SH-SY5Y and N2a cells. Moreover, miR-130a-3p was verified to target DAPK1. DAPK1 upregulation restored the inhibitory effect of miR-130a-3p elevation on SH-SY5Y and N2a cells apoptosis as well as on cerebral damage by I/R. In addition, H19 was confirmed to bind with miR-130a-3p in SH-SY5Y and N2a cells. H19 and miR-130a-3p coordinately regulated SH-SY5Y and N2a cells apoptosis as well as cerebral damage by I/R. In conclusion, H19/miR-130a-3p/DAPK1 axis regulated the pathophysiology of neonatal HIE, suggesting potential therapeutic targets for neonatal HIE treatment.