title: MicroRNA and target protein patterns reveal physiopathological features of glioma subtypes.
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.
authors.affiliation: Team7 Nanomedicine and Brain, INSERM U836, Grenoble, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Lages
authors.forename: Audrey
authors.initials: A
authors.lastname: Guttin
authors.forename: Michèle
authors.initials: M
authors.lastname: El Atifi
authors.forename: Claire
authors.initials: C
authors.lastname: Ramus
authors.forename: Hélène
authors.initials: H
authors.lastname: Ipas
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dupré
authors.forename: Delphine
authors.initials: D
authors.lastname: Rolland
authors.forename: Caroline
authors.initials: C
authors.lastname: Salon
authors.forename: Catherine
authors.initials: C
authors.lastname: Godfraind
authors.forename: Florence
authors.initials: F
authors.lastname: deFraipont
authors.forename: Mehdi
authors.initials: M
authors.lastname: Dhobb
authors.forename: Laurent
authors.initials: L
authors.lastname: Pelletier
authors.forename: Didier
authors.initials: D
authors.lastname: Wion
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Gay
authors.forename: François
authors.initials: F
authors.lastname: Berger
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Issartel
mesh_terms: D015153:Blotting, Western; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D005910:Glioma / Q000235:genetics* / Q000378:metabolism*; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D035683:MicroRNAs / Q000235:genetics*; D016133:Polymerase Chain Reaction; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; D035683:MicroRNAs; C450006:PTBP1 protein, human; D050796:STAT3 Transcription Factor; D038941:Polypyrimidine Tract-Binding Protein; C447939:SIRT1 protein, human; D056564:Sirtuin 1