Prediction of associations between microRNAs and gene expression in glioma biology

Stefan Wuchty, Dolores Arjona, Aiguo Li, Yuri Kotliarov, Jennifer Walling, Susie Ahn, Alice Zhang, Dragan Maric, Rachel Anolik, Jean Claude Zenklusen, Howard A. Fine

Research output: Contribution to journalArticle

58 Scopus citations

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.

Original languageEnglish (US)
Article numbere14681
JournalPloS one
Volume6
Issue number2
DOIs
StatePublished - 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Wuchty, S., Arjona, D., Li, A., Kotliarov, Y., Walling, J., Ahn, S., Zhang, A., Maric, D., Anolik, R., Zenklusen, J. C., & Fine, H. A. (2011). Prediction of associations between microRNAs and gene expression in glioma biology. PloS one, 6(2), [e14681]. https://doi.org/10.1371/journal.pone.0014681