Yoonhyuk Jang1, Jangsup Moon1, Soon-Tae Lee1, Jin-Sun Jun1, Tae-Joon Kim1, Jung-Ah Lim1, Byeong-Su Park1, Jung-Suk Yu1, Dong-Kyu Park1, Ah Reaum Yang1, Kyung-Ii Park2, Ki-Young Jung1, Manho Kim1, Keun-Hwa Jung1, Daejong Jeon3, Kon Chu4, Sang Kun Lee5. 1. 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. 2. Department of Neurology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea. 3. Advanced Neural Technologies, Seoul, South Korea. 4. 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. Electronic address: stemgen1@snu.ac.kr. 5. 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. Electronic address: sangkun@snu.ac.kr.
Abstract
PURPOSE: To perform comprehensive profiling of long non-coding RNAs (LncRNAs) in temporal lobe epilepsy. METHODS: 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/). RESULTS: 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. CONCLUSION: 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.
PURPOSE: To perform comprehensive profiling of long non-coding RNAs (LncRNAs) in temporal lobe epilepsy. METHODS: We performed extensive profiling of LncRNAs and mRNAs in the mousepilocarpine 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/). RESULTS: 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. CONCLUSION: LncRNAs were dysregulated in the pilocarpinemouse 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.
Authors: Dan J Hayman; Tamara Modebadze; Sarah Charlton; Kat Cheung; Jamie Soul; Hua Lin; Yao Hao; Colin G Miles; Dimitra Tsompani; Robert M Jackson; Michael D Briggs; Katarzyna A Piróg; Ian M Clark; Matt J Barter; Gavin J Clowry; Fiona E N LeBeau; David A Young Journal: Sci Rep Date: 2021-05-17 Impact factor: 4.379
Authors: Jing Gan; Qianyun Cai; Peter Galer; Dan Ma; Xiaolu Chen; Jichong Huang; Shan Bao; Rong Luo Journal: Medicine (Baltimore) Date: 2019-08 Impact factor: 1.817