Comput. Biol. Med. - Identification and analysis of the regulatory network of Myc and microRNAs from high-throughput experimental data.

Tópicos

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Resumo

As a transcription factor, c-Myc exerts significant influence in cancer development by regulating transcription of a large number of target genes including microRNAs. However, details of regulatory networks composed of Myc, microRNAs, and microRNA target genes are still unclear. Here, at system level, we built a comprehensive Myc-regulated miRNAs (Myc-miRNAs) regulatory network through the integration of experimentally validated high-throughput data and computational predictions. Using miRNA genomic information with ChIP-PET, we identified 30 Myc-miRNAs and found most of these Myc-miRNAs target genes were significantly enriched in cell cycle, apoptosis, cell proliferation GO terms and Myc-regulated signaling pathways, using gene sets enrichment analysis. We found most Myc-miRNAs involved in Myc-related cancer pathways expressed abnormally in Myc-associated tumors through the integration of diverse types of experimental data. Based upon Myc target genes identified by ChIP-chip assays, we identified that 1031 Myc-miRNAs feed-forward loops (FFLs) were significantly different from those obtained by chance; also, 11 high-quality FFLs were extracted from experimentally validated interactions. Finally, we built the miRNA-protein interaction network of experimentally validated Myc-miRNAs and discussed the more complex network composed of several FFLs networks. As shown in this study, we performed comprehensive analysis of the Myc-miRNAs regulatory network and provided potential Myc-miRNAs target genes which were involved in Myc pathway and cancer-related biological processes.

Resumo Limpo

transcript factor cmyc exert signific influenc cancer develop regul transcript larg number target gene includ microrna howev detail regulatori network compos myc microrna microrna target gene still unclear system level built comprehens mycregul mirna mycmirna regulatori network integr experiment valid highthroughput data comput predict use mirna genom inform chippet identifi mycmirna found mycmirna target gene signific enrich cell cycl apoptosi cell prolifer go term mycregul signal pathway use gene set enrich analysi found mycmirna involv mycrel cancer pathway express abnorm mycassoci tumor integr divers type experiment data base upon myc target gene identifi chipchip assay identifi mycmirna feedforward loop ffls signific differ obtain chanc also highqual ffls extract experiment valid interact final built mirnaprotein interact network experiment valid mycmirna discuss complex network compos sever ffls network shown studi perform comprehens analysi mycmirna regulatori network provid potenti mycmirna target gene involv myc pathway cancerrel biolog process

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