Cupid: simultaneous reconstruction of microRNA-target and ceRNA networks.
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ABSTRACT:
SUBMITTER: Chiu HS
PROVIDER: S-EPMC4315299 | biostudies-literature | 2015 Feb
REPOSITORIES: biostudies-literature
Publications
Cupid: simultaneous reconstruction of microRNA-target and ceRNA networks.
Chiu Hua-Sheng HS Llobet-Navas David D Yang Xuerui X Chung Wei-Jen WJ Ambesi-Impiombato Alberto A Iyer Archana A Kim Hyunjae Ryan HR Seviour Elena G EG Luo Zijun Z Sehgal Vasudha V Moss Tyler T Lu Yiling Y Ram Prahlad P Silva José J Mills Gordon B GB Califano Andrea A Sumazin Pavel P
Genome research 20141105 2
We introduce a method for simultaneous prediction of microRNA-target interactions and their mediated competitive endogenous RNA (ceRNA) interactions. Using high-throughput validation assays in breast cancer cell lines, we show that our integrative approach significantly improves on microRNA-target prediction accuracy as assessed by both mRNA and protein level measurements. Our biochemical assays support nearly 500 microRNA-target interactions with evidence for regulation in breast cancer tumors. ...[more]
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Project description:Circular RNA (circRNA), a novel class of noncoding RNAs, has been used extensively to complement transcriptome remodeling in the central nervous system, although the genomic coverage provided has rarely been studied in intracerebral hemorrhage (ICH) and is limited and fails to provide a detailed picture of the cerebral transcriptome landscape. Here, we described sequencing-based transcriptome profiling, providing comprehensive analysis of cerebral circRNA, messenger RNA (mRNA) and microRNA (miRNA) expression in ICH rats. In the study, male Sprague-Dawley rats were subjected to ICH, and next-generation sequencing of RNAs isolated from non-hemorrhagic (Sham) and hemorrhagic (ICH) rat brain samples collected 7 (early phase) and 28 (chronic phase) days after insults, was conducted. Bioinformatics analysis was performed to determine miRNA binding sites and gene ontology of circRNAs, target genes of miRNAs, as well as biological functions of mRNAs, altered after ICH. These analyses revealed different expression profiles of circRNAs, mRNAs and miRNAs in day-7 and day-28 ICH groups, respectively, compared with the Sham. In addition, the expression signature of circRNAs was more sensitive to disease progression than that of mRNAs or miRNAs. Further analysis suggested two temporally specific circRNA-miRNA-mRNA networks based on the competitive endogenous RNA theory, which had profound impacts on brain activities after ICH. In summary, these results suggested an important role for circRNAs in the pathogenesis of ICH and in reverse remodeling based on self-protection support, providing deep insights into diverse possibilities for ICH therapy through targeting circRNAs.
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Project description:BackgroundMicroRNAs (miRNAs) mediate posttranscriptional regulation of protein-coding genes by binding to the 3' untranslated region of target mRNAs, leading to translational inhibition, mRNA destabilization or degradation, depending on the degree of sequence complementarity. In general, a single miRNA concurrently downregulates hundreds of target mRNAs. Thus, miRNAs play a key role in fine-tuning of diverse cellular functions, such as development, differentiation, proliferation, apoptosis and metabolism. However, it remains to be fully elucidated whether a set of miRNA target genes regulated by an individual miRNA in the whole human microRNAome generally constitute the biological network of functionally-associated molecules or simply reflect a random set of functionally-independent genes.MethodsThe 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.ResultsAmong 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.ConclusionThe 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.
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