The cell is a highly organized system of interacting molecules including proteins, mRNAs, and miRNAs. Analyzing the cell from a systems perspective by integrating different types of data helps revealing the complexity of diseases. Although there is emerging evidence that microRNAs have a functional role in cancer, the role of microRNAs in mediating cancer progression and metastasis remains not fully explored. As the amount of available miRNA and mRNA gene expression data grows, more systematic methods combining gene expression and biological networks become necessary to explore miRNA function. In this work I integrated functional miRNA-target interactions with mRNA and miRNA expression to infer mRNA-mediated miRNA-miRNA interactions. The inferred network represents miRNA modulation through common targets. The network is used to characterize the functional role of microRNA response element (MRE) to mediate interactions between miRNAs targeting the MRE. Results revealed that miRNA-1 is a key player in regulating prostate cancer progression. 11 miRNAs were identified as diagnostic and prognostic biomarkers that act as tumor suppressor miRNAs. This work demonstrates the utility of a network analysis as opposed to differential expression to find important miRNAs that regulate prostate cancer. 1. Introduction MicroRNAs (miRNAs) are small (18–24) nucleotide long noncoding RNAs that play a major regulatory role in a broad range of biological processes and complex diseases. Since the discovery of microRNAs , they emerged as a new layer of gene regulation that dramatically influence genes by binding to its 3′UTR and inactivate it by promoting its degradation or translational repression . Computational predictions estimated that there are around 1700 miRNAs in human and each targets hundreds of mRNAs and over 50% of the human protein coding genes are regulated by miRNAs . The area of miRNA genetics has rapidly expanded from identifying miRNAs to exploring their function and their potential as therapeutic options. Several studies have demonstrated that miRNAs are key players in the initiation and progression of cancer including prostate cancer and they act as oncogenes and tumor suppressors [4–6]. Examination of prostate tumor miRNA expression has revealed widespread dysregulation of miRNAs in primary and metastatic compared with normal prostate tissue . Profiling miRNAs in various types of cancer provided evidence that miRNAs are diagnostic and prognostic biomarkers  that may stratify prostate tumors based on specific genetic profiles and thereby
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