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miR-194-5p 可作为儿童颞叶癫痫中海马神经元增殖和凋亡的潜在生物标志物进行调控。

MiR-194-5p serves as a potential biomarker and regulates the proliferation and apoptosis of hippocampus neuron in children with temporal lobe epilepsy.

机构信息

Department of Pediatric, Affiliated Hospital of Weifang Medical University, Shandong, China.

Department of Rehabilitation, Affiliated Hospital of Weifang Medical University, Shandong, China.

出版信息

J Chin Med Assoc. 2021 May 1;84(5):510-516. doi: 10.1097/JCMA.0000000000000518.

Abstract

BACKGROUND

The aim of the present study is to explore the expression level and the clinical significance of miR-194-5p to the children with temporal lobe epilepsy, and investigate its functions in regulating cell behaviors of hippocampal neurons.

METHODS

The expression level of miR-194-5p was detected in the serum of 59 temporal lobe epilepsy (TLE) children and 63 healthy children. To further study the role of miR-194-5p in the development of TLE in children, the epileptiform discharge model was established in rat hippocampal neurons to mimic TLE conditions in children. Receiver operator characteristic (ROC) curves and area under the ROC curve were established to evaluate the diagnostic value of serum microRNAs to the differentiation of the TLE group and healthy group. The influence of miR-194-5p on the proliferation and apoptosis of hippocampus neurons was examined by using MTT and flow cytometric apoptosis assay. Luciferase reporter assay was performed to confirm the target gene of miR-194-5p.

RESULTS

The result demonstrated that miR-194-5p was significantly dysregulated in plasma of TLE patients. Analysis of ROCs showed that the miR-194-5p had high specificity and sensitivity in the diagnosis of the TLE in children. The expression of miR-194-5p was found to increase in the hippocampal cells cultured in the magnesium-free medium through quantitative real-time polymerase chain reaction. Hyper-expressed of miR-194-5p reversed TLE-induced reduction for the cell viability, and inhibited the cell apoptosis induced by TLE. Insulin-like growth factor 1 receptor (IGF1R) was proved to be a direct target gene of miR-194-5p.

CONCLUSION

MiR-194-5p is a likely potential biomarker and treatment target of TLE in children. IGF1R might be involved in the regulatory role of miR-194-5p in hippocampus neuron apoptosis.

摘要

背景

本研究旨在探讨 miR-194-5p 在儿童颞叶癫痫(TLE)中的表达水平及其临床意义,并研究其在调节海马神经元细胞行为中的作用。

方法

检测 59 例 TLE 儿童和 63 例健康儿童血清中 miR-194-5p 的表达水平。为进一步研究 miR-194-5p 在儿童 TLE 发病机制中的作用,建立大鼠海马神经元癫痫样放电模型,模拟儿童 TLE 状态。绘制受试者工作特征(ROC)曲线和 ROC 曲线下面积,评价血清 microRNAs 对 TLE 组与健康组的鉴别诊断价值。采用 MTT 和流式细胞术检测 miR-194-5p 对海马神经元增殖和凋亡的影响。荧光素酶报告基因实验验证 miR-194-5p 的靶基因。

结果

结果表明,TLE 患者血浆中 miR-194-5p 明显失调。ROC 分析显示,miR-194-5p 对儿童 TLE 的诊断具有较高的特异性和敏感性。实时定量聚合酶链反应(qRT-PCR)显示,在无镁培养基中培养的海马细胞中,miR-194-5p 表达增加。过表达 miR-194-5p 可逆转 TLE 诱导的细胞活力降低,并抑制 TLE 诱导的细胞凋亡。胰岛素样生长因子 1 受体(IGF1R)被证明是 miR-194-5p 的直接靶基因。

结论

miR-194-5p 可能是儿童 TLE 的潜在生物标志物和治疗靶点。IGF1R 可能参与了 miR-194-5p 对海马神经元凋亡的调节作用。

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