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Original Article

Exp Neurobiol 2021; 30(2): 170-182

Published online April 30, 2021

© The Korean Society for Brain and Neural Sciences

Upregulation of miR-20b Protects Against Cerebral Ischemic Stroke by Targeting Thioredoxin Interacting Protein (TXNIP)

Dejiang Yang1, Yu Tan1, Huanhuan Li1, Xiaowei Zhang1, Xinming Li1 and Feng Zhou2*

1Department of Neurology, the Third Affiliated Hospital of Nanchang University, Nanchang 330008,
2Department of Neurology, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, PR. China

Correspondence to: *To whom correspondence should be addressed.
TEL: 86-0791-88862226, FAX: 86-0791-88862226

Received: September 11, 2020; Revised: February 26, 2021; Accepted: March 16, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Graphical Abstract

Keywords: Cerebral ischemic stroke, miR-20b, TXNIP, Apoptosis, Ischemic brain injury