Decreased miR-146a expression in acute ischemic stroke directly targets the Fbxl10 mRNA and is involved in modulating apoptosis

Background: miR-146a, a strong pro-apoptotic factor in some pathophysiological processes, is reported to be involved in ischemic stroke (IS), though its role remains unclear. Fbx110 is an active anti-apoptotic factor and a predicted target of miR-146a. We hypothesized that dysregulation of miR-146a contributes to ischemic injury by targeting Fbx110. Methods: Circulating miRNAs were detected by miRNA microarray and qRT-PCR. miR-146a targets were predicted using bioinformatics and confirmed with a dual luciferase reporter assay. We used an in vitro ischemic model of oxygen-glucose deprivation and reperfusion (OGD/R) to mimic cerebral ischemia/reperfusion (I/R) conditions. Expression of miR-146a, Fbx110 and Bc1212 mRNAs, and Fbx110 and Bc1212 proteins was verified by qRT-PCR and Western blotting. The effects of miR-146a on neuronal cell apoptosis were evaluated by flow cytometry. Results: A significant reduction in miR-146a expression was observed in acute ischemic stroke (AIS). A dual-luciferase reporter assay showed that Fbx110, but not Bc1212, is a target of miR-146a. Transfection with miR-146a mimics promoted apoptosis in SK-N-SH cells and significantly reduced expression of Fbx110. Conversely, miR-146a inhibition attenuated OGD/R-induced neuronal cell death and significantly up-regulated Fbx110 expression. Conclusions: miR-146a expression was significantly down-regulated in AIS, and Fbx110 was identified as a target of miR-146a. Moreover, up-regulation of Fbx110, a miR-146a target, likely protects neurons from ischemic death. (C) 2017 Elsevier Ltd. All rights reserved.