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.

MicroRNAs: Novel Regulators of Oligodendrocyte Differentiation and Potential Therapeutic Targets in Demyelination-Related Diseases

“…The global patterns of miRNA expression might be more revealing than the analysis of single miRNAs. However, the mere knowledge of the physical interaction networks between specific mRNAs and miRNAs that can be used to predict putative causal regulatory interactions in myelinating diseases is insufficient [81]. Other factors, such as Egr1, Sox11, and ErbB4 [3,82], that inhibit OL differentiation may also interact with unknown but related miRNAs; thus, further studies are needed.…”

Original article Differential expression of microRNA-210 in gliomas of variable cell origin and correlation between increased expression levels and disease progression in astrocytic tumours

“…Examples of these miRNA include: miR-21, miR-221/222, miR- 210, miR-9, miR-10(a,b), miR-15(a,b) and miR-26a. MiRNA expression can also be reduced in gliomas, acting as tumour repressors, decreasing cell growth and proliferation, migration and invasion and increasing apoptosis, such as seen with miR-181(a,b,c), miR-128, miR-451, miR-7, miR-34a, miR-124, miR-218 and miR-326 [1,14,27,33,38,44]. There have also been studies profiling miRNA levels in gliomas in order to compare and determine potential differences between tumour grades.…”

MicroRNAs as efficient biomarkers in high-grade gliomas

“…microRNA-7, downregulated in GBM [32,65], has been shown to inhibit EGFR expression, what leads to reduction in Akt phosphorylation [28]. The other targets of miRNA-7 are p21 activating kinase (PAK1) and focal adhesion kinase (FAK) microRNA-7.…”