gms | German Medical Science

57. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie (DGNN)

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie

12. - 15.09.2012, Erlangen

Banner: 57. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie

MicroRNA-132 frequently shows reduced expression in medulloblastoma and regulates the expression of Sirt1

Meeting Abstract

  • presenting/speaker Petra Zipper - Uniklinik Düsseldorf, Neuropathologie, Düsseldorf, Germany
  • Franziska Liesenberg - Uniklinik Düsseldorf, Neuropathologie, Düsseldorf, Germany
  • Anneliese Forchmann - Uniklinik Düsseldorf, Neuropathologie, Düsseldorf, Germany
  • Daniela Karra - Uniklinik Düsseldorf, Neuropathologie, Düsseldorf, Germany
  • Özlem Bolat - Uniklinik Düsseldorf, Neuropathologie, Düsseldorf, Germany
  • Guido Reifenberger - Uniklinik Düsseldorf, Neuropathologie, Düsseldorf, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Erlangen, 12.-15.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgnnOP14

DOI: 10.3205/12dgnn014, URN: urn:nbn:de:0183-12dgnn0145

Veröffentlicht: 11. September 2012

© 2012 Zipper et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

MicroRNAs (miRNAs) are small, non-coding RNAs that function as powerful post-transcriptional regulators of gene expression by translational inhibition or cleavage of target mRNAs. We investigated the potential role of altered miRNA expression in medulloblastomas, the most common malignant brain tumor in children. To identify medulloblastoma-associated miRNAs, we screened for aberrant miRNA expression in 8 medulloblastomas from Ptch1+/- mice and 10 human medulloblastomas (5 classic and 5 desmoplastic medulloblastomas) using microarray and real time-PCR analyses. Among the identified candidate miRNAs, we focused on miR-132, which has been reported to be involved in neuronal survival and differentiation. This miRNA was significantly down-regulated in murine medulloblastoma as compared to postnatal cerebellar tissue as well as in both classic and desmoplastic medulloblastomas when compared to normal human cerebellar tissue. Functional analyses of the human medulloblastoma cell line DAOY and the murine medulloblastoma cell line 2M57 revealed reduced cell viability and proliferation after transfection of miR-132 precursors. Concerning miR-132 target gene identification, we focused on SIRT1, a miR-132 target in human adipocytes, whose expression also was down-regulated in medulloblastoma cells transfected with pre-miR-132. Using 3'-UTR luciferase-reporter assay and Western blot analysis, we found that miR-132 directly regulates the expression of SIRT1 in medulloblastoma. In summary, our data indicate that expression of miR-132 is frequently down-regulated in medulloblastomas and confirm SIRT1 as a direct target in medulloblastoma cells. Overexpression of this particular miRNA causes reduced medulloblastoma cell viability and proliferation. Thus, down-regulation of miR-132 likely contributes to medulloblastoma pathogenesis.