MicroRNA-193b is a regulator of amyloid precursor protein in the blood and cerebrospinal fluid derived exosomal microRNA-193b is a biomarker of Alzheimer's disease
MicroRNA-193b is a regulator of amyloid precursor protein in the blood and cerebrospinal fluid derived exosomal microRNA-193b is a biomarker of Alzheimer's disease
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DOI：
10.3892/mmr.2014.2484
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发表时间：
2014-11-01
影响因子：
3.4
通讯作者：
Wang, Pei-Chang
中科院分区：
文献类型：
--
作者：
Liu, Chen-Geng;Song, Jing;Wang, Pei-Chang
淀粉样前体蛋白（APP）在阿尔茨海默病（AD）的发生中具有重要作用。在我们之前的研究中，我们使用microRNA（miR）阵列发现miR-193 b在9月龄APP/PS1双转基因小鼠的海马中下调。本研究通过生物信息学分析发现miR-193 b是一种可能靶向APP 3 '-非翻译区（UTR）的miR，并进一步研究了miR-193 b在APP中的功能。测量来自APP/PS1双转基因小鼠、轻度认知障碍（MCI）和阿尔茨海默型痴呆（DAT）患者的样品中的miR-193 b、外泌体miR-193 b、A β、tau、p-tau、HCY和APOE的水平。结果表明，过表达miR-193 b可抑制APP的mRNA和蛋白表达，miR-193 b抑制剂寡核苷酸可诱导APP表达上调。与对照组相比，MCI和DAT患者血液中的外泌体miR-193 b较低，但总miR-193 b不低。与MCI组相比，DAT患者血液中的外泌体miR-193 b水平较低。在DAT患者的脑脊液（CSF）中还观察到外泌体miR-193 b表达水平降低。DAT患者CSF中的外泌体miR-193 b与A β 42呈负相关。总之，这些发现表明miR-193 b可能在AD的发展中起作用，并且外泌体miR-193 b具有作为MCI和DAT患者的新型、非侵入性、基于血液的生物标志物的潜力。
Amyloid precursor protein (APP) has an important function in the generation of Alzheimer's disease (AD). In our previous study, miR-193b was found to be downregulated in the hippocampi of 9-month-old APP/PS1 double-transgenic mice using microRNA (miR) array. In the present study, bioinformatic analyses showed that miR-193b was a miR that was predicted to potentially target the 3'-untranslated region (UTR) of APP. Subsequently, the function of miR-193b on APP was studied. The levels of miR-193b, exosomal miR-193b, A beta, tau, p-tau, HCY and APOE in samples from APP/PS1 double-transgenic mice, mild cognitive impairment (MCI) and dementia of Alzheimer-type (DAT) patients, were measured. The results indicated that overexpression of miR-193b could repress the mRNA and protein expression of APP. The miR-193b inhibitor oligonucleotide induced upregulation of APP. Binding sites of miR-193b in the 3'-UTR of APP were identified by luciferase assay. MCI and DAT patients had lower exosomal miR-193b, but not total miR-193b, in the blood as compared with the controls. DAT patients had lower exosomal miR-193b levels in blood as compared with the MCI group. A decreased exosomal miR-193b expression level was additionally observed in the cerebral spinal fluid (CSF) of DAT patients. Negative correlations were found between exosomal miR-193b and A beta 42 in the CSF of DAT patients. In conclusion, these findings showed that miR-193b may function in the development of AD and exosomal miR-193b has potential as a novel, non-invasive, blood-based biomarker of MCI and DAT patients.