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65th Annual Meeting of the German Society of Neurosurgery (DGNC)

German Society of Neurosurgery (DGNC)

11 - 14 May 2014, Dresden

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miR-451 a potent switch operating tumorigenesis and neurogenesis

Meeting Abstract

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  • Ute Schäfer - Research Unit for Experimental Neurotraumatology, Department of Neurosurgery, Medical University of Graz, Graz, Austria
  • Muammer Ücal - Research Unit for Experimental Neurotraumatology, Department of Neurosurgery, Medical University of Graz, Graz, Austria
  • Daniel Hammberger - Research Unit for Experimental Neurotraumatology, Department of Neurosurgery, Medical University of Graz, Graz, Austria
  • Christa Trattnig - Research Unit for Experimental Neurotraumatology, Department of Neurosurgery, Medical University of Graz, Graz, Austria
  • Gerda Grünbacher - Research Unit for Experimental Neurotraumatology, Department of Neurosurgery, Medical University of Graz, Graz, Austria
  • Klaus Kraitsy - Research Unit for Experimental Neurotraumatology, Department of Neurosurgery, Medical University of Graz, Graz, Austria
  • Cristiana de Giuro - Research Unit for Experimental Neurotraumatology, Department of Neurosurgery, Medical University of Graz, Graz, Austria
  • Ulrike Fasching - Research Unit for Experimental Neurotraumatology, Department of Neurosurgery, Medical University of Graz, Graz, Austria
  • Gord van Campe - Department of Neurosurgery, Medical University of Graz, Graz, Austria
  • Michael Mokry - Department of Neurosurgery, Medical University of Graz, Graz, Austria
  • Johannes Haybaeck - Institute of Pathology, Medical University of Graz, Graz, Austria
  • Beate Rinner - Center of Medical Research, Medical University of Graz, Graz, Austria
  • Markus Absenger - Center of Medical Research, Medical University of Graz, Graz, Austria
  • Silke Patz - Research Unit for Experimental Neurotraumatology, Department of Neurosurgery, Medical University of Graz, Graz, Austria

Deutsche Gesellschaft für Neurochirurgie. 65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Dresden, 11.-14.05.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. DocMO.12.07

doi: 10.3205/14dgnc074, urn:nbn:de:0183-14dgnc0740

Published: May 13, 2014

© 2014 Schäfer et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: Recent evidence points to a critical role for a specific class of noncoding RNAs, called microRNAs (miRNAs) in the regulation of physiological versus pathophysiological processes. It was our aim to identify miRNAs that are key players during adult neurogenesis particularly following traumatic brain injury. miR-451 was identified to be shuttled by microparticles in the CSF of TBI patients during the acute phase. Detailed analysis of miR-451 revealed a regulatory role of this molecule in proliferation, migration and neuronal maturation.

Method: I. Analysis of miR-451 expression and regulation of expression in brain and glioblastoma: In situ hybridisation and/or qRT-PCR analysis in adult rat brains and in grade IV glioblastomas. II. Functional analysis of miR-451: Knock out mice (miR-451-/-); cellular gain and loss of function analysis; Immunohistochemistry; qRT-PCR, Western Blot analysis; proliferation and migration assays, life imaging of neuronal differentiation, life imaging of tumor migration; organotypic cortex and tumor co-cultures

Results: miR-451 is expressed in the dentate gyrus and to some extent in the cortex of adult rats and wild type mice as demonstrated by in situ hybridisation. miR-451 expression is associated with a pronounced expression of NF200 in cortical dendrites. In mir-451 knock-out mice NF200 dendrites are significantly shorter and less dense. In accordance with these results overexpression of miR-451 in neuronal stem cells induces a pronounced outgrowth of neurites. Inhibition of miR-451 expression on the other hand results in an increase of proliferation and migration of precursor cells, but prevents neurite outgrowth. Similarly a pronounced proliferation and migration of glioblastoma cells, that express miR-451 at very low levels, can be inhibited when miR-451 is overexpressed in the cells.

Conclusions: Our results indicate that miR-451 expression seems to regulate neuronal maturation processes such as dendritic outgrowth and density. On the other hand low expression levels of miR-451 seem to support the proliferative and migratory potential of neuronal precursor cells and glioblastomas. miR-451 might thereby be a potent therapeutic agent that might support late neuronal maturation process during impaired neurogenesis, ie following traumatic brain injury but it might also be implemented to inhibit pathophysiological proliferation and migration, ie in glioblastomas.