Detecting microRNAs of high influence on protein functional interaction networks: a prostate cancer case study
- Mohammed AlshalalfaAffiliated withDepartment of Computer Science, University of CalgaryBiotechnology Research Centre, Palestine Polytechnic University Email author
- , Gary D BaderAffiliated withUniversity of Toronto, and the Department of Molecular Genetics, University of Toronto
- , Anna GoldenbergAffiliated withGenetics and Genome Biology
- , Quaid MorrisAffiliated withUniversity of Toronto, and the Department of Molecular Genetics, University of Toronto
- , Reda AlhajjAffiliated withDepartment of Computer Science, University of Calgary
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.
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.
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.
KeywordsMiRNA Protein interactions Systems biology High-influence miRNA
- Detecting microRNAs of high influence on protein functional interaction networks: a prostate cancer case study
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
BMC Systems Biology
- Online Date
- August 2012
- Online ISSN
- BioMed Central
- Additional Links
- Protein interactions
- Systems biology
- High-influence miRNA
- Author Affiliations
- 1. Department of Computer Science, University of Calgary, Calgary, AB, Canada
- 4. Biotechnology Research Centre, Palestine Polytechnic University, Hebron, Palestine
- 2. University of Toronto, and the Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
- 3. Genetics and Genome Biology, Toronto, Canada