Dysregulated long non-coding RNAs in the temporal lobe epilepsy mouse model. (May 2018)

• Record Type: Journal Article
• Authors: Jang, Yoonhyuk; Moon, Jangsup; Lee, Soon-Tae; Jun, Jin-Sun; Kim, Tae-Joon; Lim, Jung-Ah; Park, Byeong-Su; Yu, Jung-Suk; Park, Dong-Kyu; Yang, Ah Reaum; Park, Kyung-II; Jung, Ki-Young; Kim, Manho; Jung, Keun-Hwa; Jeon, Daejong; Chu, Kon; Lee, Sang Kun
• Is Part Of: Seizure. Volume 58(2018)
• Page Start: 110
• Page End: 119
• Publication Date: 2018-05
• Subjects: Epilepsy -- Periodicals; Epilepsy -- Periodicals; Seizures -- Periodicals; Épilepsie -- Périodiques; Electronic journals; Electronic journals; 616.853
• DOI: 10.1016/j.seizure.2018.04.010
• Languages: English
• ISSNs: 1059-1311

Abstract

Highlights: We analyzed the LncRNAs and mRNAs in the TLE model by separating the brain parts. Ten dysregulated LncRNAs were co-dysregulated with mRNAs in the epilepsy model. The co-dysregulated mRNAs were associated with the mTOR and REST pathway. The co-dysregulated LncRNAs might be possible key regulators in epileptogenesis. 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.