MiR-130a exerts neuroprotective effects against ischemic stroke through PTEN/PI3K/AKT pathway

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Zheng, Tingting
Shi, Yu
Zhang, Jun
Peng, Jiao
Zhang, Xue
Chen, Keke
Chen, Yun
Liu, Li
Griffith University Author(s)
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2019
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https://creativecommons.org/licenses/by/4.0/
Abstract

Background: Ischemic stroke is significantly affected by the dysfunction of the miRNA network. Recent research has described that disordered expression of miR-130a is associated with ischemic stroke. Here, we aimed to investigate the possible mechanism of the miR-130a-mediated neuroprotection that follows ischemia-reperfusion (I/R) injury. Method: This study was comprised of two models: oxygen-glucose deprivation/Reperfusion (OGDR) and middle cerebral artery occlusion (MCAO). RT-PCR and immunoblotting were used to examine gene expression levels, and MTT assay and flow cytometric analysis were used to examine cell states. We also used 2, 3, 5-triphenyltetrazolium chloride (TTC) staining to assess the cerebral infarct volume. Then, we employed bioinformatics analysis and luciferase reporter assay to identify and validate the target molecule of miR-130a, PTEN. Results: Our findings indicated that miR-130a expression was lower in PC12 cells after OGDR (oxygen-glucose deprivation/reperfusion) and in rats after MCAO (middle cerebral artery occlusion). Moreover, ectopic-expression of miR-130a can significantly improve cell survival rate and reduce cell apoptosis and ROS production in PC12 cells after OGDR. In addition, re-expression of miR-130a yielded an obvious reduction in MCAO-induced infarct volume and neurological deficits in rats. Bioinformatics analysis revealed that PTEN was a miR-130a target and could overturn the effect of miR-130a on cerebral ischemia, both in vivo and in vitro. Therefore, we set out to further investigate the PTEN-affected PI3K/AKT pathway and found that upregulation of miR-130a activated the PI3K/AKT pathway. Conclusions: Our data demonstrated that miR-130a prevented cerebral I/R damage by mediating the PTEN/PI3K/AKT axis. These preliminarily findings furthered our understanding of this mechanism and identified new potential therapeutic targets for ischemic stroke.

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Biomedicine & Pharmacotherapy
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117
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© 2019 The Authors. Published by Elsevier Masson SAS. This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Pharmacology and pharmaceutical sciences
Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Pharmacology & Pharmacy
Research & Experimental Medicine
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Zheng, T; Shi, Y; Zhang, J; Peng, J; Zhang, X; Chen, K; Chen, Y; Liu, L, MiR-130a exerts neuroprotective effects against ischemic stroke through PTEN/PI3K/AKT pathway, Biomedicine & Pharmacotherapy, 2019, 117
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