Abstract
BackgroundThe 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.ResultsOur 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.ConclusionsWe 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.
Highlights
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
Positive correlation between protein connectivity and the number of miRNAs targeting the corresponding protein has been observed by Liang and Li [32]. This means that proteins with large numbers of partners in the proteins in protein interaction networks (PPIN) network need more miRNAs to control their expression. miRNA induced influence can propagate in the regulatory network by targeting master transcription factors
We show that miRNAs with high influence on protein complexes and biological processes are likely involved in cancer progression and have potential prognostic significance
Summary
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 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. Most human diseases, and cancer in particular, cannot be attributed to single gene but arise due to complex interactions among multiple components of the cell, including genes, proteins, and miRNAs [1]. Sequence-based methods provide a general view of the potential miRNA targets but expression data or other cellular context information is required to more accurately predict miRNAtarget interactions
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