Tatura Roman, Buchholz Malte, Dickson Dennis W, van Swieten John, McLean Catriona, Höglinger Günter, Müller Ulrich
Institute of Human Genetics, Justus-Liebig-University, Gießen, Germany.
Clinic for Gastroenterology, Endocrinology and Metabolism, Philipps-University, Marburg, Germany.
Neurogenetics. 2016 Jul;17(3):165-71. doi: 10.1007/s10048-016-0480-6. Epub 2016 Apr 6.
Progressive supranuclear palsy is a sporadic neurodegenerative disorder. Genetic, environmental, and possibly epigenetic factors contribute to disease. In order to better understand the potential role of epigenetic changes in progressive supranuclear palsy, we investigated whether some microRNAs and their target genes are dysregulated. We analyzed expression of 372 well-characterized microRNAs in forebrains of a total of 40 patients and of 40 controls using TaqMan arrays and SYBR Green quantitative real-time PCR. The exploratory cohort included forebrains from 20 patients and 20 controls provided by the Erasmus Medical Centre in Rotterdam, Netherlands. Confirmatory samples were from Jacksonville, Florida, and from Melbourne, Australia. Both microRNA profiling and SYBR Green quantitative real-time PCR revealed significant upregulation of miR-147 (miR-147a) and miR-518e in the exploratory cohort. Highly increased expression of these two microRNAs was validated in the confirmatory samples. Target genes of miR-147a (NF1, ACLY, ALG12) and of miR-518e (CPEB1, JAZF1, RAP1B) were repressed in patients' forebrains. The results suggest that dysregulation of specific microRNAs contributes to disease by repressing target genes involved in various cellular functions.
进行性核上性麻痹是一种散发性神经退行性疾病。遗传、环境以及可能的表观遗传因素都与该疾病的发生有关。为了更好地理解表观遗传变化在进行性核上性麻痹中的潜在作用，我们研究了某些微小RNA及其靶基因是否失调。我们使用TaqMan芯片和SYBR Green定量实时PCR分析了总共40例患者和40例对照的前脑样本中372种特征明确的微小RNA的表达情况。探索性队列包括来自荷兰鹿特丹伊拉斯姆斯医学中心的20例患者和20例对照的前脑样本。验证性样本来自美国佛罗里达州杰克逊维尔和澳大利亚墨尔本。微小RNA谱分析和SYBR Green定量实时PCR均显示，在探索性队列中miR-147（miR-147a）和miR-518e显著上调。这两种微小RNA的高表达在验证性样本中得到了证实。miR-147a（NF1、ACLY、ALG12）和miR-518e（CPEB1、JAZFⅠ、RAP1B）的靶基因在患者前脑中受到抑制。结果表明，特定微小RNA的失调通过抑制参与各种细胞功能的靶基因而导致疾病。
