Distinct Expression of Long Non-Coding RNAs in an Alzheimer's Disease Model
Distinct Expression of Long Non-Coding RNAs in an Alzheimer's Disease Model
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DOI：
10.3233/jad-142919
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发表时间：
2015-01-01
影响因子：
4
通讯作者：
Chu, Kon
中科院分区：
文献类型：
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作者：
Lee, Doo Young;Moon, Jangsup;Chu, Kon
近年来，随着全转录组分析方法的发展，许多以前未知的非编码转录本被发现。在非编码转录物中，长链非编码RNA（lncRNA）由于其调节转录调控的能力而受到越来越多的关注。虽然在阿尔茨海默病（AD）的非编码RNA的表达的改变进行了研究，大多数研究集中在参与microRNA，和lncRNA在AD中的综合表达谱一直缺乏。在这项研究中，进行微阵列分析以获得在AD的三重转基因模型（3xTg-AD）中失调的lncRNA的表达谱。总共分析了4，622个lncRNA：与对照小鼠相比，205个lncRNA在3xTg-AD中显著失调，并且230个lncRNA在3xTg-AD中以年龄依赖性方式显著失调（>= 2.0倍，p < 0.05）。其中，27和15 lncRNA，分别有相邻的蛋白质编码基因的表达也显着失调。这些lncRNA及其邻近基因中的大多数具有相同的失调方向。对于这些lncRNA和相邻基因对，重要的基因本体论术语是DNA依赖的转录调节、转录调节因子活性和胚胎器官形态发生。最高度上调的lncRNA之一具有与多个染色体区域重叠的395 bp核心序列。这是第一项全面鉴定3xTg-AD小鼠中失调的lncRNA的研究，并可能促进AD中靶向lncRNA的治疗药物的开发。
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.