Hongxue Sun1, Di Zhong2, Jing Jin3, Qingqing Liu4, Haining Wang5, Guozhong Li6. 1. Department of Neurology, The First Affiliated Hospital, Harbin Medical University, 23 You Zheng Street, Harbin 150001, Heilong Jiang Province, PR China. Electronic address: hongxues898@126.com. 2. Department of Neurology, The First Affiliated Hospital, Harbin Medical University, 23 You Zheng Street, Harbin 150001, Heilong Jiang Province, PR China. Electronic address: dityan@163.com. 3. Department of Neurology, The First Affiliated Hospital, Harbin Medical University, 23 You Zheng Street, Harbin 150001, Heilong Jiang Province, PR China. Electronic address: jinjing99999@sina.cn. 4. Department of Neurology, The First Affiliated Hospital, Harbin Medical University, 23 You Zheng Street, Harbin 150001, Heilong Jiang Province, PR China. Electronic address: 576829098@qq.com. 5. Department of Neurology, The First Affiliated Hospital, Harbin Medical University, 23 You Zheng Street, Harbin 150001, Heilong Jiang Province, PR China. Electronic address: 372273325@qq.com. 6. Department of Neurology, The First Affiliated Hospital, Harbin Medical University, 23 You Zheng Street, Harbin 150001, Heilong Jiang Province, PR China. Electronic address: lgzhrbmu1962@163.com.
Abstract
OBJECTIVE: This study investigated the role of miR-215 and nuclear factor-κB activator (Act)1 and their mechanisms of action in ischemic stroke. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVE: This study investigated the role of miR-215 and nuclear factor-κB activator (Act)1 and their mechanisms of action in ischemic stroke. METHODS: 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. RESULTS: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. CONCLUSION: 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.
Authors: Zhangli Su; Elizabeth L Frost; Catherine R Lammert; Roza K Przanowska; John R Lukens; Anindya Dutta Journal: RNA Biol Date: 2020-01-31 Impact factor: 4.652
Authors: Sheng-Peng Liu; Lei Huang; Jerry Flores; Yan Ding; Peng Li; Jun Peng; Gang Zuo; John H Zhang; Jun Lu; Ji-Ping Tang Journal: CNS Neurosci Ther Date: 2019-04-24 Impact factor: 5.243