Department of Neurology, Laboratory for Neurotherapeutics, Comprehensive Epilepsy Center, Center for Medical Innovations, Biomedical Research Institute, Seoul National University Hospital, Program in Neuroscience, Seoul National University College of Medicine, Seoul, South Korea.
Department of Neurology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea.
Seizure. 2018 May;58:110-119. doi: 10.1016/j.seizure.2018.04.010. Epub 2018 Apr 13.
To perform comprehensive profiling of long non-coding RNAs (LncRNAs) in temporal lobe epilepsy.
We performed extensive profiling of LncRNAs and mRNAs in the mouse pilocarpine model in specific brain regions, the hippocampus and cortex, and compared the results to those of the control mouse. Differentially expressed LncRNAs and mRNAs were identified with a microarray analysis (Arraystar Mouse LncRNA Expression Microarray V3.0). Then, gene ontology (GO) and pathway analysis were performed to investigate the potential roles of the differentially expressed mRNAs in the pilocarpine model. Protein-protein interactions transcribed by dysregulated mRNAs with/without co-dysregulated LncRNAs were analyzed using STRING v10 (http://string-db.org/).
A total of 22 and 83 LncRNAs were up- and down-regulated (≥2.0-fold, all P < .05), respectively, in the hippocampus of the epilepsy model, while 46 and 659 LncRNAs were up- and down-regulated, respectively, in the cortex of the epilepsy model. GO and pathway analysis revealed that the dysregulated mRNAs were closely associated with a process already known to be involved in epileptogenesis: acute inflammation, calcium ion regulation, extracellular matrix remodeling, and neuronal differentiation. Among the LncRNAs, we identified 10 LncRNAs commonly dysregulated with corresponding mRNAs in the cortex. The STRING analysis showed that the dysregulated mRNAs were interconnected around two centers: the mTOR pathway-related genes and REST pathway-related genes.
LncRNAs were dysregulated in the pilocarpine mouse model according to the brain regions of the hippocampus and cortex. The dysregulated LncRNAs with co-dysregulated mRNAs might be possible therapeutic targets for the epigenetic regulation of chronic epilepsy.
对颞叶癫痫中的长非编码 RNA（LncRNA）进行全面分析。
我们在特定脑区（海马体和皮质）的匹鲁卡品小鼠模型中广泛分析 LncRNA 和 mRNA 的表达谱，并与对照组小鼠的结果进行比较。采用微阵列分析（Arraystar Mouse LncRNA Expression Microarray V3.0）鉴定差异表达的 LncRNA 和 mRNA。然后，进行基因本体（GO）和通路分析，以研究差异表达的 mRNA 在匹鲁卡品模型中的潜在作用。使用 STRING v10（http://string-db.org/）分析由失调的 mRNA 及其共失调 LncRNA 转录的蛋白-蛋白相互作用。
癫痫模型中海马体中共有 22 个和 83 个 LncRNA 分别上调和下调（均≥2.0 倍，所有 P 值均<.05），皮质中分别有 46 个和 659 个 LncRNA 上调和下调。GO 和通路分析表明，失调的 mRNA 与已被证实参与癫痫发生的过程密切相关：急性炎症、钙离子调节、细胞外基质重塑和神经元分化。在 LncRNA 中，我们在皮质中鉴定到 10 个与相应 mRNA 共同失调的 LncRNA。STRING 分析显示，失调的 mRNA 围绕两个中心相互连接：mTOR 通路相关基因和 REST 通路相关基因。
根据海马体和皮质的脑区，匹鲁卡品小鼠模型中的 LncRNA 发生失调。失调的 LncRNA 与其共失调的 mRNA 可能是慢性癫痫表观遗传调控的潜在治疗靶点。
