miR‑15a inhibits cell apoptosis and inflammation in a temporal lobe epilepsy model by downregulating GFAP

Fan,Yuehui; Wang,Weiping; Li,Weifeng; Li,Xianjun

doi:10.3892/mmr.2020.11388

miR‑15a inhibits cell apoptosis and inflammation in a temporal lobe epilepsy model by downregulating GFAP

Authors:
- Yuehui Fan
- Weiping Wang
- Weifeng Li
- Xianjun Li
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Affiliations: Department of Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China, Department of Neurology, The First Hospital of Shijiazhuang, Shijiazhuang, Hebei 050011, P.R. China
Published online on: July 30, 2020 https://doi.org/10.3892/mmr.2020.11388
Pages: 3504-3512

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Abstract

Temporal lobe epilepsy (TLE) is a type of epilepsy, which is associated with high morbidity and recurrence rates, and is also difficult to treat. Therefore, it is important to identify novel treatments for TLE. In recent years, with the development of molecular therapies, the regulatory mechanisms and networks of microRNAs (miRNAs/miRs) have become areas of great interest in disease research. The present study aimed to determine a potential novel therapeutic target for the treatment of TLE by identifying differentially expressed miRNAs. The function of miR‑15a was verified in vivo and in vitro by constructing a rat epilepsy model and using hippocampal neurons treated with Mg2+‑free medium, respectively. The mRNA expression levels of miR‑15a, glial fibrillary acidic protein (GFAP), interleukin (IL)‑1β, IL‑6 and tumor necrosis factor α (TNF‑α) were analyzed using reverse transcription‑quantitative PCR. Furthermore, the protein expression levels of GFAP were determined using western blotting. TUNEL and flow cytometry assays were used to detect the levels of cell apoptosis both in vitro and in vivo, respectively. In addition, dual‑luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to determine the relationship between miR‑15a and GFAP. The results of the present study suggested that the expression levels of miR‑15a were downregulated in TLE tissues and epileptic cells. It was also discovered that the upregulated expression levels of miR‑15a significantly inhibited the rate of apoptosis in epileptic cells, in addition to the expression levels of IL‑1β, IL‑6 and TNF‑α in vitro and in vivo. Moreover, the dual‑luciferase reporter and RIP assays results demonstrated that miR‑15a directly targeted GFAP in hippocampal neurons. Rescue experiments indicated that increasing the expression levels of GFAP effectively attenuated the inhibitory effects of the high expression levels of miR‑15a on apoptosis and inflammation. In conclusion, the results of the present study suggested that the upregulation of miR‑15a may inhibit cell apoptosis and inflammation in TLE by targeting GFAP, thus providing a potential therapeutic target for the treatment of TLE.

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