Lee Doo Young, Moon Jangsup, Lee Soon-Tae, Jung Keun-Hwa, Park Dong-Kyu, Yoo Jung-Seok, Sunwoo Jun-Sang, Byun Jung-Ick, Lim Jung-Ah, Kim Tae-Joon, Jung Ki-Young, Kim Manho, Jeon Daejong, Chu Kon, Lee Sang Kun
Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, South Korea.
Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, South Korea; Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea.
Biochem Biophys Res Commun. 2015 Jul 10;462(4):433-40. doi: 10.1016/j.bbrc.2015.04.149. Epub 2015 May 12.
Genome-wide profiling has revealed that eukaryotic genomes are transcribed into numerous non-coding RNAs. In particular, long non-coding RNAs (lncRNAs) have been implicated in various human diseases due to their biochemical and functional diversity. Epileptic disorders have been characterized by dysregulation of epigenetic regulatory mechanisms, and recent studies have identified several lncRNAs involved in neural development and network function. However, comprehensive profiling of lncRNAs implicated in chronic epilepsy has been lacking. In this study, microarray analysis was performed to obtain the expression profile of lncRNAs dysregulated in pilocarpine and kainate models, two models of temporal lobe epilepsy commonly used for studying epileptic mechanisms. Total of 4622 lncRNAs were analyzed: 384 lncRNAs were significantly dysregulated in pilocarpine model, and 279 lncRNAs were significantly dysregulated in kainate model compared with control mice (≥3.0-fold, p < 0.05). Among these, 54 and 14 lncRNAs, respectively, had adjacent protein-coding genes whose expressions were also significantly dysregulated (≥2.0-fold, p < 0.05). Majority of these pairs of lncRNAs and adjacent genes shared the same direction of dysregulation. For the selected adjacent gene-lncRNA pairs, significant Gene Ontology terms were embryonic appendage morphogenesis and neuron differentiation. This was the first study to comprehensively identify dysregulated lncRNAs in two different models of chronic epilepsy and will likely provide a novel insight into developing lncRNA therapeutics.
全基因组分析表明，真核生物基因组可转录为大量非编码RNA。特别是，长链非编码RNA（lncRNA）因其生化和功能多样性而与多种人类疾病有关。癫痫性疾病的特征是表观遗传调控机制失调，最近的研究已经确定了几种参与神经发育和网络功能的lncRNA。然而，缺乏对慢性癫痫中lncRNA的全面分析。在本研究中，进行了微阵列分析以获得在毛果芸香碱和红藻氨酸模型中失调的lncRNA的表达谱，这两种颞叶癫痫模型常用于研究癫痫机制。总共分析了4622个lncRNA：与对照小鼠相比，在毛果芸香碱模型中有384个lncRNA显著失调，在红藻氨酸模型中有279个lncRNA显著失调（≥3.0倍，p<0.05）。其中，分别有54个和14个lncRNA具有相邻的蛋白质编码基因，其表达也显著失调（≥2.0倍，p<0.05）。这些lncRNA与相邻基因对中的大多数共享相同的失调方向。对于选定的相邻基因-lncRNA对，显著的基因本体学术语是胚胎附属器官形态发生和神经元分化。这是第一项全面鉴定两种不同慢性癫痫模型中失调lncRNA的研究，可能会为开发lncRNA疗法提供新的见解。
