Serum microRNA miR-501-3p as a potential biomarker related to the progression of Alzheimer's disease.
Serum microRNA miR-501-3p as a potential biomarker related to the progression of Alzheimer's disease.
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血清microRNA miR-501-3p作为与阿尔茨海默氏病进展有关的潜在生物标志物。
DOI：
10.1186/s40478-017-0414-z
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发表时间：
2017-01-31
影响因子：
7.1
通讯作者：
Kuwano R
中科院分区：
文献类型：
--
作者：
Hara N;Kikuchi M;Miyashita A;Hatsuta H;Saito Y;Kasuga K;Murayama S;Ikeuchi T;Kuwano R
MicroRNA（miRNAs）是一种有吸引力的分子，可用作神经退行性疾病如阿尔茨海默病（AD）的血液生物标志物之一，因为miRNAs在生物流体（包括血清或血浆）中相对稳定。为了用下一代全基因组测序确定AD的血液miRNA生物标志物，我们首先调查了45份血清样本。这些来自27名AD患者和18名对照（发现集），他们在血清采样后两周内进行尸检，并进行神经病理学诊断。我们发现，三种miRNAs，hsa-miR-501- 3 p，hsa-let-7 f-5 p和hsa-miR-26 b-5 p，在AD样品和对照之间显著失调。通过定量逆转录聚合酶链反应（PCR）在由36名临床诊断的AD患者和22名年龄匹配的认知正常对照组成的验证集中进一步证实了hsa-miR-501- 3 p的失调，其灵敏度和特异性分别为53%和100%（曲线下面积= 0.82）。AD患者血清hsa-miR-501- 3 p水平下调，其较低水平与简易精神状态检查量表评分较低显著相关。与其血清水平相反，我们发现hsa-miR-501- 3 p在从发现组尸检获得的相同供体的AD脑中显著上调。培养细胞中的hsa-miR-501- 3 p过表达，模拟了AD脑中的hsa-miR-501- 3 p上调，诱导了128个基因的显著下调，这些基因过度代表了基因本体论术语、DNA复制和有丝分裂细胞周期。我们的研究结果表明，hsa-miR-501- 3 p是一种新的血清生物标志物，可能对应于AD大脑中发生的病理事件。本文的在线版本（doi：10.1186/s40478-017-0414-z）包含补充材料，可供授权用户使用。
MicroRNAs (miRNAs) are attractive molecules to utilize as one of the blood-based biomarkers for neurodegenerative disorders such as Alzheimer’s disease (AD) because miRNAs are relatively stable in biofluid, including serum or plasma. To determine blood miRNA biomarkers for AD with next-generation sequencing genome-wide, we first surveyed 45 serum samples. These came from 27 AD patients and 18 controls (discovery set) that underwent autopsy within two weeks after their serum sampling and were neuropathologically diagnosed. We found that three miRNAs, hsa-miR-501-3p, hsa-let-7f-5p, and hsa-miR-26b-5p, were significantly deregulated between the AD samples and the controls. The deregulation for hsa-miR-501-3p was further confirmed by quantitative reverse transcription polymerase chain reaction (PCR) in a validation set composed of 36 clinically diagnosed AD patients and 22 age-matched cognitively normal controls with a sensitivity and specificity of 53% and 100%, respectively (area under the curve = 0.82). Serum hsa-miR-501-3p levels were downregulated in AD patients, and its lower levels significantly correlated with lower Mini-Mental State Examination scores. Contrary to its serum levels, we found that hsa-miR-501-3p was remarkably upregulated in the same donors’ AD brains obtained at autopsy from the discovery set. The hsa-miR-501-3p overexpression in cultured cells, which mimicked the hsa-miR-501-3p upregulation in the AD brains, induced significant downregulation of 128 genes that overrepresented the Gene Ontology terms, DNA replication, and the mitotic cell cycle. Our results suggest that hsa-miR-501-3p is a novel serum biomarker that presumably corresponds to pathological events occurring in AD brains. The online version of this article (doi:10.1186/s40478-017-0414-z) contains supplementary material, which is available to authorized users.