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KMID : 0892920210300020170
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Experimental Neurobiology
2021 Volume.30 No. 2 p.170 ~ p.182
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Upregulation of miR-20b Protects Against Cerebral Ischemic Stroke by Targeting Thioredoxin Interacting Protein (TXNIP)
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Yang Dejiang
Tan Yu
Li Huanhuan
Zhang Xiaowei
Li Xinming
Zhou Feng
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Abstract
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Dysregulation of microRNAs (miRNAs) is involved in abnormal development and pathophysiology in the brain. Although miR-20b plays essential roles in various human diseases, its function in cerebral ischemic stroke remains unclear. A cell model of oxygen glucose deprivation/reoxygenation (OGD/R) and A rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) were constructed. qRT-PCR and western blot were used to evaluate the expression of miR-20b and TXNIP. Cell viability was detected by MTT assay, and cell apoptosis was evaluated by flow cytometry. Targetscan and Starbase were used to predict the potential targets of miR-20b. Luciferase reporter assay was applied to determine the interaction between miR-20b and TXNIP. Rescue experiments were conducted to confirm the functions of miR-20b/TXNIP axis in cerebral ischemic stroke. MiR-20b was significantly downregulated after I/R both in vitro and in vivo . Upregulation of miR-20b inhibited OGD/R-induced neurons apoptosis and attenuated ischemic brain injury in rat model. Bioinformatic prediction suggested that TXNIP might be a target of miR-20b, and luciferase reporter assay revealed that miR-20b negatively regulated TXNIP expression by directly binding to the 3’-UTR of TXNIP. Downregulation of TXNIP inhibited OGD/R-induced neurons apoptosis in vitro and ischemic brain injury in vivo . Rescue experiments indicated that downregulation of TXNIP effectively reversed the effect of miR-20b inhibitor in neurons apoptosis after OGD/R-treatment and ischemic brain injury in a mouse model after MCAO/R-treatment. Our study demonstrated that upregulation of miR-20b protected the brain from ischemic brain injury by targeting TXNIP, extending our understanding of miRNAs in cerebral ischemic stroke.
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KEYWORD
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Cerebral ischemic stroke, miR-20b, TXNIP, Apoptosis, Ischemic brain injury
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