Bandyopadhyay et al. Silence 2010, 1:6 http://www.silencejournal.com/content/1/1/6 Open Access RESEARCH © 2010 Bandyopadhyay et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and repro- duction in any medium, provided the original work is properly cited. Research Development of the human cancer microRNA network Sanghamitra Bandyopadhyay* 1 , Ramkrishna Mitra 1 , Ujjwal Maulik 2 and Michael Q Zhang 3,4 Abstract Background: MicroRNAs are a class of small noncoding RNAs that are abnormally expressed in different cancer cells. Molecular signature of miRNAs in different malignancies suggests that these are not only actively involved in the pathogenesis of human cancer but also have a significant role in patients survival. The differential expression patterns of specific miRNAs in a specific cancer tissue type have been reported in hundreds of research articles. However limited attempt has been made to collate this multitude of information and obtain a global perspective of miRNA dysregulation in multiple cancer types. Results: 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. Conclusions: 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 relationships in the proposed network model. These raise many unaddressed issues in miRNA research that have never been reported previously. These observations are expected to have an intense implication in cancer and may be useful for further research. Background A family of approximately 22 nucleotide (nt) noncoding RNAs termed microRNAs (miRNAs) has been identified in eukaryotic organisms ranging from nematodes to humans [1-3]. Caenorhabditis elegans (C. elegans) lin-4 and let-7 are the first discovered miRNAs [4-6]. Increas- ing evidence indicates that miRNAs are key regulators of various fundamental biological processes such as prolif- eration, apoptosis, differentiation, and so on [7]. For example let-7 family miRNAs identified in C. elegans, Drosophila, Zebrafish or Human [5,8,9] have important roles for terminal differentiation in normal embryonic development, temporal upregulation and so on. In let-7 mutants, stem cells can fail to exit the cell cycle and ter- * Correspondence: sanghami@isical.ac.in 1 Machine Intelligence Unit, Indian Statistical Institute, Kolkata, India