Increased microRNA-34c abundance in Alzheimer's disease circulating blood plasma.

Increased microRNA-34c abundance in Alzheimer's disease circulating blood plasma.
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DOI:
10.3389/fnmol.2014.00002
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发表时间:
2014
影响因子:
4.8
通讯作者:
Wang E
Wang E
中科院分区:
医学2区
文献类型:
--
作者:
Bhatnagar S;Chertkow H;Schipper HM;Yuan Z;Shetty V;Jenkins S;Jones T;Wang E

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循环 microRNA 存在于细胞成分、外周血单核细胞 (PBMC) 或无细胞血浆中,已成为许多器官中与年龄相关的系统性、疾病相关变化的生物标志物。此前,我们已经证明阿尔茨海默病(AD)患者循环 PBMC 中的 microRNA (miR)-34a 增加。在本研究中,我们发现,与正常年龄匹配的对照相比,这种 microRNA 的姐妹 miR-34c 在 AD 循环血液样本的细胞和血浆成分中表现出更大的增加。统计分析显示,通过受试者工作特征(ROC)分析测定的 miR-34c 水平的准确性:曲线下面积为 0.99(p < 0.0001),95% 置信水平从 0.97 延伸至 1。根据简易精神状态检查(MMSE)定义,miR-34c 水平与轻度和中度 AD 之间的 Pearson 相关性显示 r 值为 -0.7,表明相对两个参数之间存在很强的反比关系。这些数据表明,AD 中 microRNA 34c 的血浆水平比其姐妹 miR-34a 或 PBMC 中的自身水平要显着得多。转染研究表明,miR-34c 与其姐妹 miR-34a 一样,抑制培养细胞中涉及细胞存活和氧化防御途径的几个选定基因的表达,例如 Bcl2、SIRT1 等。综上所述,我们的结果表明,与年龄匹配的正常对照相比,PBMC 和血浆中 miR-34c 水平的增加可能反映了 AD 患者循环血液样本的变化。
Circulating microRNAs, present either in the cellular component, peripheral blood mononuclear cells (PBMC), or in cell-free plasma, have emerged as biomarkers for age-dependent systemic, disease-associated changes in many organs. Previously, we have shown that microRNA (miR)-34a is increased in circulating PBMC of Alzheimer's disease (AD) patients. In the present study, we show that this microRNA's sister, miR-34c, exhibits even greater increase in both cellular and plasma components of AD circulating blood samples, compared to normal age-matched controls. Statistical analysis shows the accuracy of levels of miR-34c assayed by receiver operating characteristic (ROC) analysis: the area under the curve is 0.99 (p < 0.0001) and the 95% confidence level extends from 0.97 to 1. Pearson correlation between miR-34c levels and mild and moderate AD, as defined by the mini-mental state examination (MMSE), shows an r-value of −0.7, suggesting a relatively strong inverse relationship between the two parameters. These data show that plasma levels of microRNA 34c are much more prominent in AD than those of its sister, miR-34a, or than its own level in PBMC. Transfection studies show that miR-34c, as does its sister miR-34a, represses the expression of several selected genes involved in cell survival and oxidative defense pathways, such as Bcl2, SIRT1, and others, in cultured cells. Taken together, our results indicate that increased levels of miR-34c in both PBMC and plasma may reflect changes in circulating blood samples in AD patients, compared to age-matched normal controls.
循环miR34a作为用于脑衰老的无创,无创的生物标志物。
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