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

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.