title: Distinct Expression of Long Non-Coding RNAs in an Alzheimer's Disease Model.
abstract: With the recent advancement in transcriptome-wide profiling approach, numerous non-coding transcripts previously unknown have been identified. Among the non-coding transcripts, long non-coding RNAs (lncRNAs) have received increasing attention for their capacity to modulate transcriptional regulation. Although alterations in the expressions of non-coding RNAs have been studied in Alzheimer's disease (AD), most research focused on the involvement of microRNAs, and comprehensive expression profiling of lncRNAs in AD has been lacking. In this study, microarray analysis was performed to procure the expression profile of lncRNAs dysregulated in a triple transgenic model of AD (3xTg-AD). A total of 4,622 lncRNAs were analyzed: 205 lncRNAs were significantly dysregulated in 3xTg-AD compared with control mice, and 230 lncRNAs were significantly dysregulated within 3xTg-AD in an age-dependent manner (≥2.0-fold, p < 0.05). Among these, 27 and 15 lncRNAs, respectively, had adjacent protein-coding genes whose expressions were also significantly dysregulated. A majority of these lncRNAs and their adjacent genes shared the same direction of dysregulation. For these pairs of lncRNAs and adjacent genes, significant Gene Ontology terms were DNA-dependent regulation of transcription, transcription regulator activity, and embryonic organ morphogenesis. One of the most highly upregulated lncRNAs had a 395 bp core sequence that overlapped with multiple chromosomal regions. This is the first study that comprehensively identified dysregulated lncRNAs in 3xTg-AD mice and will likely facilitate the development of therapeutics targeting lncRNAs in AD.
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Doo Young
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Department of Neurology, Biomedical Research Institute, 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.
authors.forename: Jangsup
authors.initials: J
authors.lastname: Moon
authors.affiliation: Department of Neurology, Biomedical Research Institute, 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.
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.affiliation: Department of Neurology, Biomedical Research Institute, 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.
authors.forename: Keun-Hwa
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Park
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Jung-Seok
authors.initials: JS
authors.lastname: Yoo
authors.affiliation: Department of Neurology, Biomedical Research Institute, 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.
authors.forename: Jun-Sang
authors.initials: JS
authors.lastname: Sunwoo
authors.affiliation: Department of Neurology, Biomedical Research Institute, 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.
authors.forename: Jung-Ick
authors.initials: JI
authors.lastname: Byun
authors.affiliation: Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Shin
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Daejong
authors.initials: D
authors.lastname: Jeon
authors.affiliation: Department of Neurology, Biomedical Research Institute, 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.
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Jung
authors.affiliation: Department of Neurology, Biomedical Research Institute, 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 Protein Metabolism Medical Research Center, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Neurology, Biomedical Research Institute, 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.
authors.forename: Sang Kun
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Neurology, Biomedical Research Institute, 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.
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics*; D063990:Gene Ontology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046228:Microarray Analysis; D009154:Mutation / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D016875:tau Proteins / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D016875:tau Proteins
keywords: 3xTg-AD; Alzheimer's disease; gene ontology; long non-coding RNAs; microarray