The miRNome of Alzheimer's disease: consistent downregulation of the miR-132/212 cluster

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• 作者：Sabrina Pichler^a ; ^{sabrina.pichler@uks.eu} ; Wei Gu^a ; ^b ; Daniela Hartl^a ; Gilles Gasparoni^a ; Petra Leidinger^c ; Andreas Keller^d ; Eckart Meese^c ; Manuel Mayhaus^a ; Harald Hampel^e ; ^f ; Matthias Riemenschneider^a ; ^g
• 关键词：Alzheimer's disease ; Human cortical brain tissue ; microRNA ; mRNA ; Hsa-miR-132 ; Hsa-miR-212
• 刊名：Neurobiology of Aging
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：50
• 期：Complete
• 页码：167.e1-167.e10
• 全文大小：779 K
• 卷排序：50

文摘

MicroRNAs (miRNAs) are small noncoding RNA molecules, with essential functions in RNA silencing and post-transcriptional regulation of gene expression. miRNAs appear to regulate the development and function of the nervous system. Alterations of miRNA expression have been associated with Alzheimer's disease (AD). To characterize the AD miRNA signature, we examined genome-wide miRNA and mRNA expression patterns in the temporal cortex of AD and control samples. We validated our miRNA results by semiquantitative real-time polymerase chain reaction (PCR) in independent prefrontal cortex. Furthermore, we separated gray and white matter brain sections to identify the cellular origin of the altered miRNA expression. We observed genome-wide downregulation of hsa-miR-132-3p and hsa-miR-212-3p in AD with a stronger decrease in gray matter AD samples. We further identified 10 differently expressed transcripts achieving genome-wide levels of significance. Significantly deregulated miRNAs and mRNAs were correlated and examined for potential binding sites (in silico). This miRNome-wide study in AD provides supportive evidence and corroborates an important contribution of miR-132/212 and corresponding target mRNAs to the pathogenesis of AD.