Abstract
Acting as a class of regulators of gene expression, miRNAs play crucial roles in various biological processes, such as cell proliferation, differentiation, and apoptosis. Increasing evidence indicates that dysregulation of miRNA expression and function is related to the pathogenesis of many human diseases. Here, we applied an integration strategy to identify conserved miRNA co-expression relationships and constructed a miRNA co-expression network based on human and mouse miRNA expression data. We performed large-scale bioinformatics analyses of conserved miRNA co-expression relationships and their functional links and confirmed that these conserved co-expressed miRNA relationships in the network tend to be functionally relevant. Co-expressed miRNA pairs regulated by common TFs are significantly enriched within the same miRNA clusters and/or miRNA families. Mapping well-known disease miRNAs to the network, we identified three miRNA sub-networks that are highly related to cancer risk. Furthermore, we observed that these conserved co-expressed miRNA sub-networks cooperatively regulate cancer-related functions through synergistically repressing crucial components of these processes. Our results suggest that co-expressed miRNAs assist to drive the initiation and progression of cancer in a cooperative manner.
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