miR‑135a‑5p inhibitor protects glial cells against apoptosis via targeting SIRT1 in epilepsy

Wang,Ying; Yang,Zhiquan; Zhang,Kai; Wan,Yi; Zhou,Yu; Yang,Zhuanyi

doi:10.3892/etm.2021.9848

miR‑135a‑5p inhibitor protects glial cells against apoptosis via targeting SIRT1 in epilepsy

Authors:
- Ying Wang
- Zhiquan Yang
- Kai Zhang
- Yi Wan
- Yu Zhou
- Zhuanyi Yang
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Affiliations: Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: February 26, 2021 https://doi.org/10.3892/etm.2021.9848
Article Number: 431
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Epilepsy is a common neurological disease that can induce severe physiological brain damage, including nerve cell apoptosis. MicroRNAs (miRs) have been widely investigated in epilepsy therapy. miR‑135a‑5p expression levels in children with temporal lobe epilepsy were found to be significantly increased. However, whether miR‑135a‑5p participates in epilepsy‑induced cell apoptosis is not completely understood. In the present study, an in vitro model of epilepsy in BV2 microglia cells was induced using 6‑µm kainic acid (KA). Reverse‑transcription quantitative PCR was performed to analyze miR‑135a‑5p and sirtuin 1 (SIRT1) mRNA expression levels. Western blotting was performed to measure SIRT1 protein expression levels. BV2 cell proliferation and apoptosis were assessed by performing MTT assays and flow cytometry, respectively. A BCA protein assay kit was used to detect caspase‑3 and caspase‑9 activities. TargetScan and dual luciferase reporter assays were performed to investigate the interaction between miR‑135a‑5p and the 3'‑untranslated region (UTR) of SIRT1. miR‑135a‑5p expression was significantly increased in the KA‑induced in vitro model of epilepsy in BV2 microglia. miR‑135a‑5p inhibitor effectively promoted BV2 microglia proliferation and inhibited microglia apoptosis, whereas small interfering RNA targeting SIRT1 significantly repressed BV2 microglia proliferation and induced microglia apoptosis. In addition, the results demonstrated that the 3'‑UTR of SIRT1 mRNA was targeted by miR‑135a‑5p, and SIRT1 knockdown attenuated miR‑135a‑5p inhibitor‑mediated effects on epilepsy. In summary, the results of the present study identified the role of miR‑135a‑5p inhibitor pretreatment in protecting nerve cells against epilepsy‑induced apoptosis and provided a novel strategy for the treatment of neural damage in seizures.

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