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LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression

(2012) NATURE GENETICS. 44(11). p.1199-1206
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Abstract
LIN28B regulates developmental processes by modulating microRNAs (miRNAs) of the let-7 family. A role for LIN28B in cancer has been proposed but has not been established in vivo. Here, we report that LIN28B showed genomic aberrations and extensive overexpression in high-risk neuroblastoma compared to several other tumor entities and normal tissues. High LIN28B expression was an independent risk factor for adverse outcome in neuroblastoma. LIN28B signaled through repression of the let-7 miRNAs and consequently resulted in elevated MYCN protein expression in neuroblastoma cells. LIN28B-let-7-MYCN signaling blocked differentiation of normal neuroblasts and neuroblastoma cells. These findings were fully recapitulated in a mouse model in which LIN28B expression in the sympathetic adrenergic lineage induced development of neuroblastomas marked by low let-7 miRNA levels and high MYCN protein expression. Interference with this pathway might offer therapeutic perspectives.
Keywords
COPY NUMBER DEFECTS, HUMAN HEPATOCELLULAR-CARCINOMA, TUMOR-SUPPRESSOR, CELL-PROLIFERATION, PROMOTES TRANSFORMATION, RISK STRATIFICATION, MIRNA EXPRESSION, MESSENGER-RNA, IN-VIVO, N-MYC

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MLA
Molenaar, Jan J, Raquel Domingo-Fernández, Marli E Ebus, et al. “LIN28B Induces Neuroblastoma and Enhances MYCN Levels via Let-7 Suppression.” NATURE GENETICS 44.11 (2012): 1199–1206. Print.
APA
Molenaar, J. J., Domingo-Fernández, R., Ebus, M. E., Lindner, S., Koster, J., Drabek, K., Mestdagh, P., et al. (2012). LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression. NATURE GENETICS, 44(11), 1199–1206.
Chicago author-date
Molenaar, Jan J, Raquel Domingo-Fernández, Marli E Ebus, Sven Lindner, Jan Koster, Ksenjia Drabek, Pieter Mestdagh, et al. 2012. “LIN28B Induces Neuroblastoma and Enhances MYCN Levels via Let-7 Suppression.” Nature Genetics 44 (11): 1199–1206.
Chicago author-date (all authors)
Molenaar, Jan J, Raquel Domingo-Fernández, Marli E Ebus, Sven Lindner, Jan Koster, Ksenjia Drabek, Pieter Mestdagh, Peter van Sluis, Linda J Valentijn, Johan van Nes, Marloes Broekmans, Franciska Haneveld, Richard Volckmann, Isabella Bray, Lukas Heukamp, Annika Sprüssel, Theresa Thor, Kristina Kieckbusch, Ludger Klein-Hitpass, Matthias Fischer, Jo Vandesompele, Alexander Schramm, Max M van Noesel, Luigi Varesio, Franki Speleman, Angelika Eggert, Raymond L Stallings, Huib N Caron, Rogier Versteeg, and Johannes H Schulte. 2012. “LIN28B Induces Neuroblastoma and Enhances MYCN Levels via Let-7 Suppression.” Nature Genetics 44 (11): 1199–1206.
Vancouver
1.
Molenaar JJ, Domingo-Fernández R, Ebus ME, Lindner S, Koster J, Drabek K, et al. LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression. NATURE GENETICS. 2012;44(11):1199–206.
IEEE
[1]
J. J. Molenaar et al., “LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression,” NATURE GENETICS, vol. 44, no. 11, pp. 1199–1206, 2012.
@article{3171566,
  abstract     = {LIN28B regulates developmental processes by modulating microRNAs (miRNAs) of the let-7 family. A role for LIN28B in cancer has been proposed but has not been established in vivo. Here, we report that LIN28B showed genomic aberrations and extensive overexpression in high-risk neuroblastoma compared to several other tumor entities and normal tissues. High LIN28B expression was an independent risk factor for adverse outcome in neuroblastoma. LIN28B signaled through repression of the let-7 miRNAs and consequently resulted in elevated MYCN protein expression in neuroblastoma cells. LIN28B-let-7-MYCN signaling blocked differentiation of normal neuroblasts and neuroblastoma cells. These findings were fully recapitulated in a mouse model in which LIN28B expression in the sympathetic adrenergic lineage induced development of neuroblastomas marked by low let-7 miRNA levels and high MYCN protein expression. Interference with this pathway might offer therapeutic perspectives.},
  author       = {Molenaar, Jan J and Domingo-Fernández, Raquel and Ebus, Marli E and Lindner, Sven and Koster, Jan and Drabek, Ksenjia and Mestdagh, Pieter and van Sluis, Peter and Valentijn, Linda J and van Nes, Johan and Broekmans, Marloes and Haneveld, Franciska and Volckmann, Richard and Bray, Isabella and Heukamp, Lukas and Sprüssel, Annika and Thor, Theresa and Kieckbusch, Kristina and Klein-Hitpass, Ludger and Fischer, Matthias and Vandesompele, Jo and Schramm, Alexander and van Noesel, Max M and Varesio, Luigi and Speleman, Franki and Eggert, Angelika and Stallings, Raymond L and Caron, Huib N and Versteeg, Rogier and Schulte, Johannes H},
  issn         = {1061-4036},
  journal      = {NATURE GENETICS},
  keywords     = {COPY NUMBER DEFECTS,HUMAN HEPATOCELLULAR-CARCINOMA,TUMOR-SUPPRESSOR,CELL-PROLIFERATION,PROMOTES TRANSFORMATION,RISK STRATIFICATION,MIRNA EXPRESSION,MESSENGER-RNA,IN-VIVO,N-MYC},
  language     = {eng},
  number       = {11},
  pages        = {1199--1206},
  title        = {LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression},
  url          = {http://dx.doi.org/10.1038/ng.2436},
  volume       = {44},
  year         = {2012},
}

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