MiR-130a exerts neuroprotective effects against ischemic stroke through PTEN/PI3K/AKT pathway
Authors: Xue Zhang
Tingting Zheng
Keke Chen
Li Liu
Jun Zhang
Yu Shi
Yun Chen
Jiao Peng
Journal: Biomedicine & Pharmacotherapy (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Cerebral ischemia-reperfusion; PI3K/AKT pathway; PTEN; miR-130a.
Affiliations: Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen Peking University- The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, Guangdong Province, PR China., Queensland Micro- and Nanotechnology Centre, Griffith University, Brisbane, QLD 4111, Australia., Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, PR China., Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen Peking University- The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, Guangdong Province, PR China. Electronic address: .

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. 

Retracted: No

PubPeer comments:
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