Upregulation of miR-215 exerts neuroprotection effects against ischemic injury via negative regulation of Act1/IL-17RA signaling.

Abstract

This study investigated the role of miR-215 and nuclear factor-κB activator (Act)1 and their mechanisms of action in ischemic stroke. Cell viability was examined with the 3-(4,5-dimethythiazol-. 2-yl)-2,5-diphenyl tetrazolium bromide assay; cell apoptosis was detected by flow cytometry; and mRNA and protein expression was assessed by quantitative real-time PCR and western blotting, respectively. A mouse model of middle cerebral artery occlusion (MCAO) was treated with or without miR-215 mimic to verify the in vitro results. The relationship between miR-215 and interleukin (IL)-17 was evaluated in human peripheral blood from 29 patients. Act1 was upregulated whereas miR-215 was downregulated in ischemic stroke. Overexpression of miR-215 by transfection of a mimic repressed Act1 protein levels in vitro and in vivo, although the luciferase assay showed that miR-215 did not directly bind to the 3' untranslated region of Act1. MiR-215 overexpression inhibited cell apoptosis and autophagy. Increasing miR-215 levels reduced ischemic infarction and improved neurological deficit, while loss of miR-215 phenocopied the effects of IL-17. Upregulation of miR-215 exerts neuroprotection against ischemic injury by negatively regulating Act1/IL-17 receptor A signaling. These findings provide potential therapeutic targets for the treatment of ischemic stroke.