Wang Zhe, Xu Panpan, Chen Biyue, Zhang Zheyu, Zhang Chunhu, Zhan Qiong, Huang Siqi, Xia Zi-An, Peng Weijun
Department of Integrated Traditional Chinese and Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Aging (Albany NY). 2018 Apr 27;10(4):775-788. doi: 10.18632/aging.101427.
Alzheimer's disease (AD) is the most common form of dementia worldwide. Accumulating evidence indicates that non-coding RNAs are strongly implicated in AD-associated pathophysiology. However, the role of these ncRNAs remains largely unknown. In the present study, we used microarray analysis technology to characterize the expression patterns of circular RNAs (circRNAs), microRNAs (miRNAs), and mRNAs in hippocampal tissue from Aβ-induced AD model rats, to integrate interaction data and thus provide novel insights into the mechanisms underlying AD. A total of 555 circRNAs, 183 miRNAs and 319 mRNAs were identified to be significantly dysregulated (fold-change ≥ 2.0 and -value < 0.05) in the hippocampus of AD rats. Quantitative real-time polymerase chain reaction (qRT-PCR) was then used to validate the expression of randomly-selected circRNAs, miRNAs and mRNAs. Next, GO and KEGG pathway analyses were performed to further investigate ncRNAs biological functions and potential mechanisms. In addition, we constructed circRNA-miRNA and competitive endogenous RNA (ceRNA) regulatory networks to determine functional interactions between ncRNAs and mRNAs. Our results suggest the involvement of different ncRNA expression patterns in the pathogenesis of AD. Our findings provide a novel perspective for further research into AD pathogenesis and might facilitate the development of novel therapeutics targeting ncRNAs.
阿尔茨海默病（AD）是全球最常见的痴呆形式。越来越多的证据表明，非编码RNA与AD相关的病理生理学密切相关。然而，这些非编码RNA的作用仍 largely unknown。在本研究中，我们使用微阵列分析技术来表征Aβ诱导的AD模型大鼠海马组织中环状RNA（circRNA）、微小RNA（miRNA）和信使RNA（mRNA）的表达模式，整合相互作用数据，从而为AD潜在机制提供新的见解。共鉴定出555种circRNA、183种miRNA和319种mRNA在AD大鼠海马中显著失调（倍数变化≥2.0且P值<0.05）。然后使用定量实时聚合酶链反应（qRT-PCR）验证随机选择的circRNA、miRNA和mRNA的表达。接下来，进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析，以进一步研究非编码RNA的生物学功能和潜在机制。此外，我们构建了circRNA-miRNA和竞争性内源RNA（ceRNA）调控网络，以确定非编码RNA与mRNA之间的功能相互作用。我们的结果表明不同的非编码RNA表达模式参与了AD的发病机制。我们的发现为进一步研究AD发病机制提供了新的视角，并可能促进针对非编码RNA的新型治疗方法的开发。
