MYCN/c-MYC-induced microRNAs repress coding gene networks associated with poor outcome in MYCN/c-MYC-activated tumors
| Autor: | Jo Vandesompele, Rosa Noguera, K. De Preter, Franki Speleman, Alexander Schramm, Candy Kumps, Genevieve Laureys, Filip Pattyn, Johannes H. Schulte, Frank Westermann, Daniel Muth, Pieter Mestdagh, Erik Fredlund, Angelika Eggert, Stefanie Schlierf, Joëlle Vermeulen, N. Van Roy |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Medizin Genes myc Biology Neuroblastoma RNA interference Cell Line Tumor microRNA Gene expression Genetics medicine Gene silencing Humans Gene Regulatory Networks Gene Silencing RNA Small Interfering Promoter Regions Genetic neoplasms Molecular Biology Regulation of gene expression Oncogene Proteins N-Myc Proto-Oncogene Protein Nuclear Proteins medicine.disease Gene Expression Regulation Neoplastic MicroRNAs Treatment Outcome Cancer research Chromatin immunoprecipitation N-Myc Transcription Factors |
| Zdroj: | Oncogene. 29(9) |
| ISSN: | 1476-5594 |
| Popis: | Increased activity of MYC protein-family members is a common feature in many cancers. Using neuroblastoma as a tumor model, we established a microRNA (miRNA) signature for activated MYCN/c-MYC signaling in two independent primary neuroblastoma tumor cohorts and provide evidence that c-MYC and MYCN have overlapping functions. On the basis of an integrated approach including miRNA and messenger RNA (mRNA) gene expression data we show that miRNA activation contributes to widespread mRNA repression, both in c-MYC- and MYCN-activated tumors. c-MYC/MYCN-induced miRNA activation was shown to be dependent on c-MYC/MYCN promoter binding as evidenced by chromatin immunoprecipitation. Finally, we show that pathways, repressed through c-MYC/MYCN miRNA activation, are highly correlated to tumor aggressiveness and are conserved across different tumor entities suggesting that c-MYC/MYCN activate a core set of miRNAs for cooperative repression of common transcriptional programs related to disease aggressiveness. Our results uncover a widespread correlation between miRNA activation and c-MYC/MYCN-mediated coding gene expression modulation and further substantiate the overlapping functions of c-MYC and MYCN in the process of tumorigenesis. |
| Databáze: | OpenAIRE |
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