MicroRNA-379-5p targets MAP3K2 to reduce autophagy and alleviate neuronal injury following cerebral ischemia via the JNK/c-Jun signaling pathway

Abstract

MicroRNAs (miRNAs) are abundant in neurons and play key roles in the function and development of the nervous system. This study focuses on the function of miR-379-5p in neurological function recovery during ischemic stroke. The expression of miR-379-5p in the serum of patients with ischemic stroke was determined. Human cerebral cortical neuron cells (HCN-2) were subjected to oxygen/glucose deprivation (OGD) to mimic an ischemic stroke in vitro, whereas mice subjected to middle cerebral artery occlusion (MCAO) were used as an animal model. The serum of patients with ischemic stroke and OGD-treated HCN-2 cells displayed a poor expression of miR-379-5p. Upregulation of miR-379-5p reduced the OGD-induced cell damage and decreased the expression of the autophagy marker protein Beclin1 in cells. Rapamycin, an autophagy activator, blocked the protective functions of miR-379-5p. Further, miR-379-5p directly bound to MAP3K2. MAP3K2 activated the JNK/c-Jun signaling pathway and suppressed the neuroprotective events mediated by miR-379-5p. The in vitro results were reproduced in vivo, where upregulation of miR-379-5p reduced neurological impairment and infarct size in MCAO-induced mice. This study suggested that miR-379-5p showed a neuroprotective effect on ischemic stroke and reduced autophagy of neurons through the suppression of MAP3K2 and the JNK/c-Jun axis.