Detecting microRNAs of high influence on protein functional interaction networks: a prostate cancer case study

BMC Systems Biology

Reda Alhajj¹  Quaid Morris³  Anna Goldenberg²  Gary D Bader³  Mohammed Alshalalfa⁴ 

[1] Department of Computer Science, University of Calgary, Calgary, AB, Canada;Genetics and Genome Biology, Toronto, Canada;University of Toronto, and the Department of Molecular Genetics, University of Toronto, Toronto ON, Canada;Biotechnology Research Centre, Palestine Polytechnic University, Hebron, Palestine

关键词: High-influence miRNA;    Systems biology;    Protein interactions;    MiRNA;   

Others  :  1143662
DOI  :  10.1186/1752-0509-6-112

 received in 2012-05-23, accepted in 2012-08-14,  发布年份 2012

【 摘 要 】

Background

The use of biological molecular network information for diagnostic and prognostic purposes and elucidation of molecular disease mechanism is a key objective in systems biomedicine. The network of regulatory miRNA-target and functional protein interactions is a rich source of information to elucidate the function and the prognostic value of miRNAs in cancer. The objective of this study is to identify miRNAs that have high influence on target protein complexes in prostate cancer as a case study. This could provide biomarkers or therapeutic targets relevant for prostate cancer treatment.

Results

Our findings demonstrate that a miRNA’s functional role can be explained by its target protein connectivity within a physical and functional interaction network. To detect miRNAs with high influence on target protein modules, we integrated miRNA and mRNA expression profiles with a sequence based miRNA-target network and human functional and physical protein interactions (FPI). miRNAs with high influence on target protein complexes play a role in prostate cancer progression and are promising diagnostic or prognostic biomarkers. We uncovered several miRNA-regulated protein modules which were enriched in focal adhesion and prostate cancer genes. Several miRNAs such as miR-96, miR-182, and miR-143 demonstrated high influence on their target protein complexes and could explain most of the gene expression changes in our analyzed prostate cancer data set.

Conclusions

We describe a novel method to identify active miRNA-target modules relevant to prostate cancer progression and outcome. miRNAs with high influence on protein networks are valuable biomarkers that can be used in clinical investigations for prostate cancer treatment.

【 授权许可】

   
2012 Alshalalfa et al.; licensee BioMed Central Ltd.

【 图 表 】

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