MicroRNA‑217 inhibition relieves cerebral ischemia/reperfusion injury by targeting SIRT1

Rao,Gaofeng; Zhang,Wenfu; Song,Shegeng

doi:10.3892/mmr.2019.10317

MicroRNA‑217 inhibition relieves cerebral ischemia/reperfusion injury by targeting SIRT1

Authors:
- Gaofeng Rao
- Wenfu Zhang
- Shegeng Song
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Affiliations: Department of Rehabilitation Medicine, The First People's Hospital of Wenling, The Affiliated Wenling Hospital of Wenzhou Medical University, Wenling, Zhejiang 317500, P.R. China
Published online on: May 31, 2019 https://doi.org/10.3892/mmr.2019.10317
Pages: 1221-1229
Copyright: © Rao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNAs (miRs) have been proposed to be involved in the pathological processes of cerebral ischemia/reperfusion (CIR) injury. The present study aimed to investigate the potential role and molecular mechanisms of miR‑217 in the regulation of neuronal survival in CIR injury. To perform the investigation, an in vitro cellular model of CIR injury was established by treating neurons with oxygen‑glucose deprivation and reoxygenation (OGD/R). miR‑217 levels in neurons were detected using reverse transcription‑quantitative PCR. The association between miR‑217 and sirtuin 1 (SIRT1) was identified using TargetScan and validated in a dual‑luciferase reporter assay. Cell viability and apoptosis were measured using a Cell Counting Kit‑8 assay and flow cytometry, respectively. The release of lactate dehydrogenase, and the production of proinflammatory factors and oxidative stress biomarkers were analyzed by ELISAs and using specific assay kits. It was revealed that miR‑217 was significantly upregulated in OGD/R‑treated neurons. SIRT1 was a direct target of miR‑217, and was downregulated in neurons following OGD/R treatment. Downregulation of miR‑217 significantly ameliorated OGD/R‑induced neuronal injury, inflammatory responses and oxidative stress. The effects of miR‑217 inhibitor on OGD/R treated neurons were attenuated by SIRT1 knockdown. Additionally, western blotting revealed that the SIRT1/AMP‑activated protein kinase‑α/NF‑κB pathway was partially involved in the regulation of OGD/R‑induced neuronal injury by miR‑217. In conclusion, the data of the present study indicated that the downregulation of miR‑217 protected neurons against OGD/R‑induced injury by targeting SIRT1.

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