MicroRNA and target protein patterns reveal physiopathological features of glioma subtypes

PLoS One. 2011;6(5):e20600. doi: 10.1371/journal.pone.0020600. Epub 2011 May 31.

Abstract

Gliomas such as oligodendrogliomas (ODG) and glioblastomas (GBM) are brain tumours with different clinical outcomes. Histology-based classification of these tumour types is often difficult. Therefore the first aim of this study was to gain microRNA data that can be used as reliable signatures of oligodendrogliomas and glioblastomas. We investigated the levels of 282 microRNAs using membrane-array hybridisation and real-time PCR in ODG, GBM and control brain tissues. In comparison to these control tissues, 26 deregulated microRNAs were identified in tumours and the tissue levels of seven microRNAs (miR-21, miR-128, miR-132, miR-134, miR-155, miR-210 and miR-409-5p) appropriately discriminated oligodendrogliomas from glioblastomas. Genomic, epigenomic and host gene expression studies were conducted to investigate the mechanisms involved in these deregulations. Another aim of this study was to better understand glioma physiopathology looking for targets of deregulated microRNAs. We discovered that some targets of these microRNAs such as STAT3, PTBP1 or SIRT1 are differentially expressed in gliomas consistent with deregulation of microRNA expression. Moreover, MDH1, the target of several deregulated microRNAs, is repressed in glioblastomas, making an intramitochondrial-NAD reduction mediated by the mitochondrial aspartate-malate shuttle unlikely. Understanding the connections between microRNAs and bioenergetic pathways in gliomas may lead to identification of novel therapeutic targets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Hypoxia / genetics
  • Cell Hypoxia / physiology
  • Cell Line, Tumor
  • CpG Islands / genetics
  • DNA Methylation / genetics
  • Glioma / genetics*
  • Glioma / metabolism*
  • Heterogeneous-Nuclear Ribonucleoproteins / genetics
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism
  • Humans
  • In Vitro Techniques
  • MicroRNAs / genetics*
  • Polymerase Chain Reaction
  • Polypyrimidine Tract-Binding Protein / genetics
  • Polypyrimidine Tract-Binding Protein / metabolism
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism

Substances

  • Heterogeneous-Nuclear Ribonucleoproteins
  • MicroRNAs
  • PTBP1 protein, human
  • STAT3 Transcription Factor
  • Polypyrimidine Tract-Binding Protein
  • SIRT1 protein, human
  • Sirtuin 1