MicroRNA Interaction network in human: implications of clustered microRNA in biological pathways and genetic diseases

A novel group of small non-coding RNA, known as microRNA (miRNA) is predicted to regulate as high as 90% of the coding genes in human. The diversity and abundance of miRNA targets offer an enormous level of combinatorial possibilities and suggest that miRNAs and their targets form a complex regulatory network. In the present study, we analyzed 711 miRNAs and their 34, 525 predicted targets in the miRBase database (http://microrna.sanger.ac.uk/, version 10 ), which generate a complex bipartite network having numerous numbers of genes forming the hub. Genes at the hub (total 9877) are significantly over represented in genes with specific molecular functions, biological processes and biological pathways as revealed from the analysis using PANTHER (http://www.pantherdb.org/genes/). We further construct a miRNA co-target network by linking every pair of miRNAs which co-target at least one gene. The weight of the link, which is taken to be the number of co-targets of the pair of miRNAs vary widely, and we could erase several links while keeping the relevant features of the network intact. The largest connected sub-graph, thus obtained, contains 479 miRNAs. More than 75% of the miRNAs deregulated in 15 different diseases collected from published data are found to be in this largest sub graph. We further analyze this sub-graph to obtain 70 small clusters containing total 330 miRNAs of 479. We identified the biological pathways where the co-targeted genes in the clusters are significantly overrepresented in comparison to that obtained with that are not co-targeted by the miRNAs in the cluster. Using published data, we identified that specific clusters of miRNAs are associated with specific diseases by altering particular pathways. We propose that instead of single miRNA, clusters of miRNA that co-targets the genes are important for the regulation of miRNA in diseases.