Prediction of Associations between microRNAs and Gene Expression in Glioma Biology
Open Access
- 16 February 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (2), e14681
- https://doi.org/10.1371/journal.pone.0014681
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.Keywords
This publication has 54 references indexed in Scilit:
- In Silico Analysis of Kinase Expression Identifies WEE1 as a Gatekeeper against Mitotic Catastrophe in GlioblastomaCancer Cell, 2010
- The interplay between transcription factors and microRNAs in genome‐scale regulatory networksBioEssays, 2009
- MicroRNAs: Target Recognition and Regulatory FunctionsCell, 2009
- MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteinsProceedings of the National Academy of Sciences of the United States of America, 2008
- A microRNA component of the p53 tumour suppressor networkNature, 2007
- Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTRProceedings of the National Academy of Sciences of the United States of America, 2007
- Transactivation of miR-34a by p53 Broadly Influences Gene Expression and Promotes ApoptosisMolecular Cell, 2007
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005
- Combinatorial microRNA target predictionsNature Genetics, 2005
- Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA TargetsCell, 2005