Comprehensive analysis of human microRNA target networks

The complete set of human miRNAs was downloaded from miRBase Release 16. We explored target genes of individual miRNA by using the Diana-microT 3.0 target prediction program, and selected the genes with the miTG score ≧ 20 as the set of highly reliable targets. Then, Entrez Gene IDs of miRNA target genes were uploaded onto KeyMolnet, a tool for analyzing molecular interactions on the comprehensive knowledgebase by the neighboring network-search algorithm. The generated network, compared side by side with human canonical networks of the KeyMolnet library, composed of 430 pathways, 885 diseases, and 208 pathological events, enabled us to identify the canonical network with the most significant relevance to the extracted network.Among 1,223 human miRNAs examined, Diana-microT 3.0 predicted reliable targets from 273 miRNAs. Among them, KeyMolnet successfully extracted molecular networks from 232 miRNAs. The most relevant pathway is transcriptional regulation by transcription factors RB/E2F, the disease is adult T cell lymphoma/leukemia, and the pathological event is cancer.The predicted targets derived from approximately 20% of all human miRNAs constructed biologically meaningful molecular networks, supporting the view that a set of miRNA targets regulated by a single miRNA generally constitute the biological network of functionally-associated molecules in human cells.MicroRNAs (miRNAs) are a class of endogenous small noncoding RNAs conserved through the evolution. They mediate posttranscriptional regulation of protein-coding genes by binding to the 3' untranslated region (3'UTR) of target mRNAs, leading to translational inhibition, mRNA destabilization or degradation, depending on the degree of sequence complementarity [1]. During the biogenesis of miRNAs, the primary miRNAs (pri-miRNAs) are transcribed from the intra- and inter-genetic regions of the genome by RNA polymerase II, followed by processing by the RNase III enzyme Drosha into pre-miRNAs. After nuclear expor