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

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Abstract

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.

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Acknowledgments

This work was supported by a grant (#518-14) from CurePSP and an ANR-BMBF-funded project on “Epigenomics of Parkinson’s disease” to G.H. and U.M. G.H. is funded by the Deutsche Forschungsgemeinschaft (DFG, HO2402/6-2).

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Authors and Affiliations

  1. Institute of Human Genetics, Justus-Liebig-University, Gießen, Germany

    Roman Tatura & Ulrich Müller

  2. Clinic for Gastroenterology, Endocrinology and Metabolism, Philipps-University, Marburg, Germany

    Malte Buchholz

  3. Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA

    Dennis W. Dickson

  4. Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands

    John van Swieten

  5. Alfred Anatomical Pathology and NNF, Victoria Brain Bank, Carlton, Australia

    Catriona McLean

  6. Department of Neurology, Technical University and German Center for Neurodegenerative Diseases (DZNE), Munich, Germany

    Günter Höglinger

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  1. Roman Tatura
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  2. Malte Buchholz
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  3. Dennis W. Dickson
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  5. Catriona McLean
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  6. Günter Höglinger
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  7. Ulrich Müller
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Correspondence to Ulrich Müller.

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Conflict of interest

The authors declare that they have no conflicts of interest. All analyzed brain samples were supplied by established brain banks (Rotterdam, Netherlands; Jacksonville, Florida; Melbourne, Australia).

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Tatura, R., Buchholz, M., Dickson, D.W. et al. microRNA profiling: increased expression of miR-147a and miR-518e in progressive supranuclear palsy (PSP). Neurogenetics 17, 165–171 (2016). https://doi.org/10.1007/s10048-016-0480-6

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  • DOI: https://doi.org/10.1007/s10048-016-0480-6

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