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

Pieter Mestdagh UGent, E Fredlund, Filip Pattyn UGent, JH Schulte, D Muth, Joëlle Vermeulen UGent, Candy Kumps UGent, S Schlierf, Katleen De Preter UGent and Nadine Van Roy UGent, et al. (2010) ONCOGENE. 29(9). p.1394-1404
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
PATHWAY DEREGULATION, TRANSCRIPTIONAL REPRESSION, EXPRESSION SIGNATURES, neuroblastoma, microRNA, c-MYC, MYCN, B-CELL LYMPHOMAS, C-MYC, N-MYC, NEUROBLASTOMA, DIFFERENTIATION, TARGET, GROWTH
journal title
ONCOGENE
Oncogene
volume
29
issue
9
pages
1394 - 1404
Web of Science type
Article
Web of Science id
000275170600014
JCR category
ONCOLOGY
JCR impact factor
7.414 (2010)
JCR rank
15/181 (2010)
JCR quartile
1 (2010)
ISSN
0950-9232
DOI
10.1038/onc.2009.429
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
833560
handle
http://hdl.handle.net/1854/LU-833560
date created
2010-01-22 09:22:11
date last changed
2012-03-13 12:55:36
@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},
  keyword      = {PATHWAY DEREGULATION,TRANSCRIPTIONAL REPRESSION,EXPRESSION SIGNATURES,neuroblastoma,microRNA,c-MYC,MYCN,B-CELL LYMPHOMAS,C-MYC,N-MYC,NEUROBLASTOMA,DIFFERENTIATION,TARGET,GROWTH},
  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},
}

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.