构建并分析颞叶癫痫大鼠模型中失调 lncRNA 相关 ceRNA 网络。
Construction and analysis of a dysregulated lncRNA-associated ceRNA network in a rat model of temporal lobe epilepsy.
机构信息
Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, PR China; Neurology Institute of Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, PR China; Neurology Institute of Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
出版信息
Seizure. 2019 Jul;69:105-114. doi: 10.1016/j.seizure.2019.04.010. Epub 2019 Apr 15.
PURPOSE
The aim of this work was to investigate expression and cross-talk between long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) in a rat model of temporal lobe epilepsy (TLE).
METHODS
Noncoding RNA chips were used to explore the expression and relationship between lncRNAs and miRNAs in a rat model of TLE. The expression of different lncRNAs and mRNAs was analysed by Pearson's correlation coefficient, and the function of each lncRNA was annotated by co-expressed genes based on gene ontology classification using DAVID. MiRNA-lncRNA interactions were predicted by using StarBase v2.0, and the competing endogenous RNA (ceRNA) relationship between lncRNAs and miRNAs was built by using Cytoscape software. Real-time PCR was used to verify chip results.
RESULTS
According to the expression profile analysis, 54 lncRNAs, 36 miRNAs and 122 mRNAs were dysregulated in TLE rat model compared to normal controls. The functions of lncRNAs in epilepsy were annotated by their co-expressed genes based on the "guilt by association" strategy. DAVID analysis revealed that differentially expressed lncRNA functions were involved in "potassium channel activity", "metal ion transmembrane transporter activity", and "voltage-gated potassium channel activity". Based on the ceRNA theory, 13 mRNAs, 10 miRNAs and 11 lncRNAs comprise the lncRNA-miRNA-mRNA ceRNA relationship in epilepsy.
CONCLUSIONS
The molecular functions of the differentially expressed genes play an important role in the pathogenesis of voltage-gated potassium channel activity. Further ceRNA analyses suggest that modulation of lncRNAs could emerge as a promising therapeutic target for TLE.
目的
本研究旨在探讨长链非编码 RNA（lncRNA）与 microRNA（miRNA）在颞叶癫痫（TLE）大鼠模型中的表达及相互作用。
方法
采用非编码 RNA 芯片技术探讨 TLE 大鼠模型中 lncRNA 与 miRNA 的表达及其相关性。采用 Pearson 相关系数分析不同 lncRNA 和 mRNAs 的表达情况，并根据基因本体分类，利用 DAVID 注释 co-expressed 基因中每个 lncRNA 的功能。通过 StarBase v2.0 预测 miRNA-lncRNA 相互作用，利用 Cytoscape 软件构建 lncRNA 和 miRNA 之间的竞争性内源 RNA（ceRNA）关系。采用实时 PCR 验证芯片结果。
结果
根据表达谱分析，与正常对照组相比，TLE 大鼠模型中 54 个 lncRNA、36 个 miRNA 和 122 个 mRNA 表达失调。根据“关联定罪”策略，基于 co-expressed 基因对癫痫相关 lncRNA 的功能进行注释。DAVID 分析显示，差异表达的 lncRNA 功能涉及“钾通道活性”、“金属离子跨膜转运活性”和“电压门控钾通道活性”。基于 ceRNA 理论，包含在癫痫 ceRNA 关系中的 lncRNA-miRNA-mRNA 有 13 个 mRNA、10 个 miRNA 和 11 个 lncRNA。
结论
差异表达基因的分子功能在电压门控钾通道活性的发病机制中起重要作用。进一步的 ceRNA 分析表明，lncRNA 的调节可能成为 TLE 的一个有前途的治疗靶点。
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