title: Prediction of Associations between microRNAs and Gene Expression in Glioma Biology.
abstract: Despite progress in the determination of miR interactions, their regulatory role in cancer is only beginning to be unraveled. Utilizing gene expression data from 27 glioblastoma samples we found that the mere knowledge of physical interactions between specific mRNAs and miRs can be used to determine associated regulatory interactions, allowing us to identify 626 associated interactions, involving 128 miRs that putatively modulate the expression of 246 mRNAs. Experimentally determining the expression of miRs, we found an over-representation of over(under)-expressed miRs with various predicted mRNA target sequences. Such significantly associated miRs that putatively bind over-expressed genes strongly tend to have binding sites nearby the 3'UTR of the corresponding mRNAs, suggesting that the presence of the miRs near the translation stop site may be a factor in their regulatory ability. Our analysis predicted a significant association between miR-128 and the protein kinase WEE1, which we subsequently validated experimentally by showing that the over-expression of the naturally under-expressed miR-128 in glioma cells resulted in the inhibition of WEE1 in glioblastoma cells.
authors.affiliation: Neuro-Oncology Branch, National Cancer Institute, National Institutes of Neurological Disorder and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wuchty
authors.forename: Dolores
authors.initials: D
authors.lastname: Arjona
authors.forename: Aiguo
authors.initials: A
authors.lastname: Li
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kotliarov
authors.forename: Jennifer
authors.initials: J
authors.lastname: Walling
authors.forename: Susie
authors.initials: S
authors.lastname: Ahn
authors.forename: Alice
authors.initials: A
authors.lastname: Zhang
authors.forename: Dragan
authors.initials: D
authors.lastname: Maric
authors.forename: Rachel
authors.initials: R
authors.lastname: Anolik
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Zenklusen
authors.forename: Howard A
authors.initials: HA
authors.lastname: Fine
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics; D002478:Cells, Cultured; D016000:Cluster Analysis; D019295:Computational Biology; D005544:Forecasting / Q000379:methods; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D046228:Microarray Analysis; D009687:Nuclear Proteins / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D014162:Transfection; D015854:Up-Regulation; D054928:Validation Studies as Topic
chemical_list: D018797:Cell Cycle Proteins; C545189:MIRN128 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human