Up-regulation of miR-122 protects against neuronal cell death in ischemic stroke through the heat shock protein 70-dependent NF- κB pathway by targeting FOXO3.

Up-regulation of miR-122 protects against neuronal cell death in ischemic stroke through the heat shock protein 70-dependent NF-κB pathway by targeting FOXO3. Exp Cell Res. 2018 Apr 28;: Authors: Guo D, Ma J, Li T, Yan L Abstract Dysfunction of the microRNA (miR) network has been emerging as a main regulator in ischemic stroke. Recently, studies have linked the deregulation of miR-122 to ischemic stroke. However, the specific role and molecular mechanism of miR-122 in ischemic stroke remain to be further investigated. Here, we found that miR-122 was decreased in mouse N2A neuroblastoma (N2A) cells after oxygen-glucose deprivation (OGD) and mouse brain after transient middle cerebral artery occlusion (MCAO). OGD treatment significantly increased N2A cell death and Caspase-3 activity, and decreased Bcl-2 protein expression. In addition, MCAO treatment induced severe mouse brain infarction, mitochondrial reactive oxygen species (ROS) production, and long-term neurological deficit. Gain-of-miR-122 function significantly suppressed OGD- and MCAO-induced injures in vitro and in vivo. Subsequently, miR-122 was validated to directly bind to the predicted 3'-untranslated region (3'-UTR) of FOXO3 gene, and the inhibitory effects of miR-122 on ischemic injury in vitro and in vivo were overturned by FOXO3 overexpression. Moreover, our results further revealed that miR-122-FOXO3 axis functioned via the heat shock protein 70 (HSP-70)-mediated NF-...
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research