microRNA profiling: increased expression of miR-147a and miR-518e in progressive supranuclear palsy (PSP)

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• 作者：Roman Tatura ; Malte Buchholz ; Dennis W. Dickson ; John van Swieten…
• 刊名：neurogenetics
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：17
• 期：3
• 页码：165-171
• 全文大小：530 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Neurosciences
  Human Genetics
  Molecular Medicine
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1364-6753
• 卷排序：17

文摘

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.KeywordsProgressive supranuclear palsy microRNAmiRTaqManSYBR GreenBrain