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MYCN/c-MYC-induced microRNAs repress coding gene networks associated with poor outcome in MYCN/c-MYC-activated tumors

(2010) ONCOGENE. 29(9). p.1394-1404
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Abstract
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.
Keywords
PATHWAY DEREGULATION, TRANSCRIPTIONAL REPRESSION, EXPRESSION SIGNATURES, neuroblastoma, microRNA, c-MYC, MYCN, B-CELL LYMPHOMAS, C-MYC, N-MYC, NEUROBLASTOMA, DIFFERENTIATION, TARGET, GROWTH

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Chicago
Mestdagh, Pieter, E Fredlund, Filip Pattyn, JH Schulte, D Muth, Joëlle Vermeulen, Candy Kumps, et al. 2010. “MYCN/c-MYC-induced microRNAs Repress Coding Gene Networks Associated with Poor Outcome in MYCN/c-MYC-activated Tumors.” Oncogene 29 (9): 1394–1404.
APA
Mestdagh, P., Fredlund, E., Pattyn, F., Schulte, J., Muth, D., Vermeulen, J., Kumps, C., et al. (2010). MYCN/c-MYC-induced microRNAs repress coding gene networks associated with poor outcome in MYCN/c-MYC-activated tumors. ONCOGENE, 29(9), 1394–1404.
Vancouver
1.
Mestdagh P, Fredlund E, Pattyn F, Schulte J, Muth D, Vermeulen J, et al. MYCN/c-MYC-induced microRNAs repress coding gene networks associated with poor outcome in MYCN/c-MYC-activated tumors. ONCOGENE. 2010;29(9):1394–404.
MLA
Mestdagh, Pieter, E Fredlund, Filip Pattyn, et al. “MYCN/c-MYC-induced microRNAs Repress Coding Gene Networks Associated with Poor Outcome in MYCN/c-MYC-activated Tumors.” ONCOGENE 29.9 (2010): 1394–1404. Print.
@article{833560,
  abstract     = {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.},
  author       = {Mestdagh, Pieter and Fredlund, E and Pattyn, Filip and Schulte, JH and Muth, D and Vermeulen, Jo{\"e}lle and Kumps, Candy and Schlierf, S and De Preter, Katleen and Van Roy, Nadine and Noguera, R and Laureys, Genevieve and Schramm, A and Eggert, A and Westermann, F and Speleman, Franki and Vandesompele, Jo},
  issn         = {0950-9232},
  journal      = {ONCOGENE},
  language     = {eng},
  number       = {9},
  pages        = {1394--1404},
  title        = {MYCN/c-MYC-induced microRNAs repress coding gene networks associated with poor outcome in MYCN/c-MYC-activated tumors},
  url          = {http://dx.doi.org/10.1038/onc.2009.429},
  volume       = {29},
  year         = {2010},
}

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