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Silence 2010
Development of the human cancer microRNA networkAbstract: In this article a cancer-miRNA network is developed by mining the literature of experimentally verified cancer-miRNA relationships. This network throws up several new and interesting biological insights which were not evident in individual experiments, but become evident when studied in the global perspective. From the network a number of cancer-miRNA modules have been identified based on a computational approach to mine associations between cancer types and miRNAs. The modules that are generated based on these association are found to have a number of common predicted target onco/tumor suppressor genes. This suggests a combinatorial effect of the module associated miRNAs on target gene regulation in selective cancer tissues or cell lines. Moreover, neighboring miRNAs (group of miRNAs that are located within 50 kb of genomic location) of these modules show similar dysregulation patterns suggesting common regulatory pathway. Besides this, neighboring miRNAs may also show a similar dysregulation patterns (differentially coexpressed) in the cancer tissues. In this study, we found that in 67% of the cancer types have at least two neighboring miRNAs showing downregulation which is statistically significant (P < 10-7, Randomization test). A similar result is obtained for the neighboring miRNAs showing upregulation in specific cancer type. These results elucidate the fact that the neighboring miRNAs might be differentially coexpressed in cancer tissues as that of the normal tissue types. Additionally, cancer-miRNA network efficiently detect hub miRNAs dysregulated in many cancer types and identify cancer specific miRNAs. Depending on the expression patterns, it is possible to identify those hubs that have strong oncogenic or tumor suppressor characteristics.Limited work has been done towards revealing the fact that a number of miRNAs can control commonly altered regulatory pathways. However, this becomes immediately evident by accompanying the analysis of cancer-miRNA rela
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