Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity
Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity
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DOI：
10.1182/blood-2010-09-299719
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发表时间：
2011-05-12
期刊：
影响因子：
20.3
通讯作者：
Bray, Paul F.
中科院分区：
文献类型：
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作者：
Nagalla, Srikanth;Shaw, Chad;Bray, Paul F.
MicroRNAs （miRNAs）通过改变蛋白质表达来调节细胞生理，但血小板miRNAs的生物学在很大程度上尚未被探索。我们利用19名健康受试者的血小板RNA进行全基因组分析，以检验血小板miRNA水平是否与血小板反应性相关。我们发现人类血小板表达284种miRNAs。miRNA谱的无监督分层聚类导致两组受试者似乎通过血小板聚集表型聚类。74个mirna在受试者之间的差异表达（DE）根据血小板聚集到肾上腺素分组，其中一个子集预测血小板反应性反应。利用这些受试者的全基因组mRNA表达数据，我们计算生成了一个高优先级的miRNA-mRNA对列表，其中DE血小板mirna在DE mRNA的3'-非翻译区具有结合位点，并且水平呈负相关。从这个列表中选择了三个miRNA-mRNA对（miR-200b: PRKAR2B， miR-495: KLHL5和miR-107: CLOCK），所有3个mirna都从靶mRNA中敲低蛋白表达。缺乏PRKAR2B的血小板活化减少支持了这些发现。综上所述，(1)血小板miRNA能够抑制血小板蛋白的表达；(2)miRNA谱与血小板反应性相关，并可能预测血小板反应性；(3)生物信息学方法可以成功鉴定血小板中的功能性miRNA。[血液杂志];2011;117(19):5189-5197]
MicroRNAs (miRNAs) regulate cell physiology by altering protein expression, but the biology of platelet miRNAs is largely unexplored. We tested whether platelet miRNA levels were associated with platelet reactivity by genome-wide profiling using platelet RNA from 19 healthy subjects. We found that human platelets express 284 miRNAs. Unsupervised hierarchical clustering of miRNA profiles resulted in 2 groups of subjects that appeared to cluster by platelet aggregation phenotypes. Seventy-four miRNAs were differentially expressed (DE) between subjects grouped according to platelet aggregation to epinephrine, a subset of which predicted the platelet reactivity response. Using whole genome mRNA expression data on these same subjects, we computationally generated a high-priority list of miRNA-mRNA pairs in which the DE platelet miRNAs had binding sites in 3'-untranslated regions of DE mRNAs, and the levels were negatively correlated. Three miRNA-mRNA pairs (miR-200b: PRKAR2B, miR-495: KLHL5, and miR-107: CLOCK) were selected from this list, and all 3 miRNAs knocked down protein expression from the target mRNA. Reduced activation from platelets lacking PRKAR2B supported these findings. In summary, (1) platelet miRNAs are able to repress expression of platelet proteins, (2) miRNA profiles are associated with and may predict platelet reactivity, and (3) bioinformatic approaches can successfully identify functional miRNAs in platelets. (Blood. 2011; 117(19):5189-5197)