Joint genome-wide profiling of miRNA and mRNA expression in Alzheimer's disease cortex reveals altered miRNA regulation.
Joint genome-wide profiling of miRNA and mRNA expression in Alzheimer's disease cortex reveals altered miRNA regulation.
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DOI：
10.1371/journal.pone.0008898
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发表时间：
2010-02-01
期刊：
影响因子：
3.7
通讯作者：
Zhou XJ
中科院分区：
文献类型：
--
作者：
Nunez-Iglesias J;Liu CC;Morgan TE;Finch CE;Zhou XJ
尽管人们对microrna在癌症及其发展中的作用进行了广泛的研究，但对其在阿尔茨海默病（AD）中的作用知之甚少。在这项研究中，我们使用微阵列首次联合分析了AD和年龄匹配的对照组大脑皮层中miRNAs和mrna的表达。这些数据为研究正常和AD大脑中miRNA和mRNA表达之间的关系提供了独特的机会。使用非参数分析，我们发现许多mirna的水平可以与其靶mrna的水平呈正相关或负相关。与独立癌症数据集的比较分析表明，这种miRNA-mRNA表达相关性不是静态的，而是与环境相关的。随后，我们确定了大量的miRNA- mrna关联，这些关联在AD与对照组中发生了变化，突出了AD在miRNA调控系统中的特异性变化。我们的研究结果表明，大脑中mirna的水平与其靶标之间存在着密切的关系。这对阿尔茨海默病的分子病理学研究以及一般的miRNA生物学都有意义。
Although microRNAs are being extensively studied for their involvement in cancer and development, little is known about their roles in Alzheimer's disease (AD). In this study, we used microarrays for the first joint profiling and analysis of miRNAs and mRNAs expression in brain cortex from AD and age-matched control subjects. These data provided the unique opportunity to study the relationship between miRNA and mRNA expression in normal and AD brains. Using a non-parametric analysis, we showed that the levels of many miRNAs can be either positively or negatively correlated with those of their target mRNAs. Comparative analysis with independent cancer datasets showed that such miRNA-mRNA expression correlations are not static, but rather context-dependent. Subsequently, we identified a large set of miRNA-mRNA associations that are changed in AD versus control, highlighting AD-specific changes in the miRNA regulatory system. Our results demonstrate a robust relationship between the levels of miRNAs and those of their targets in the brain. This has implications in the study of the molecular pathology of AD, as well as miRNA biology in general.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
miRNAMAP：哺乳动物基因组中microRNA基因及其靶基因的基因组图。
影响因子：
14.9
作者：
Hsu, Paul W. C.;Huang, Hsien-Da;Hsu, Sheng-Da;Lin, Li-Zen;Tsou, Ann-Ping;Tseng, Ching-Ping;Stadler, Peter F.;Washietl, Stefan;Hofacker, Ivo L.
通讯作者：
Hofacker, Ivo L.
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.1073/pnas.0710263105
发表时间：
2008-04-29
影响因子：
11.1
作者：
Hebert, Sebastien S.;Horre, Katrien;De Strooper, Bart
通讯作者：
De Strooper, Bart
影响因子：
5.7
作者：
Blower, Paul E.;Verducci, Joseph S.;Sadee, Wolfgang
通讯作者：
Sadee, Wolfgang