Advanced search
1 file | 1.08 MB Add to list

Monoallelic but not biallelic loss of Dicer1 promotes tumorigenesis in vivo

Irina Lambertz (UGent) , David Nittner (UGent) , Pieter Mestdagh (UGent) , Geertrui Denecker (UGent) , Jo Vandesompele (UGent) , MA Dyer and Jean-Christophe Marine (UGent)
(2010) CELL DEATH AND DIFFERENTIATION. 17(4). p.633-641
Author
Organization
Abstract
Human tumors are characterized by widespread reduction in microRNA (miRNA) expression, although it is unclear how such changes come about and whether they have an etiological role in the disease. Importantly, miRNA knockdown has been shown to enhance the tumorigenic potential of human lung adenocarcinoma cells. A defect in miRNA processing is one possible mechanism for global downregulation. To explore this possibility in more detail in vivo, we have manipulated Dicer1 gene dosage in a mouse model of retinoblastoma. We show that although monoallelic loss of Dicer1 does not affect normal retinal development, it dramatically accelerates tumor formation on a retinoblastoma-sensitized background. Importantly, these tumors retain one wild-type Dicer1 allele and exhibit only a partial decrease in miRNA processing. Accordingly, in silico analysis of human cancer genome data reveals frequent hemizygous, but not homozygous, deletions of DICER1. Strikingly, complete loss of Dicer1 function in mice did not accelerate retinoblastoma formation. miRNA profiling of these tumors identified members of the let-7 and miR-34 families as candidate tumor suppressors in retinoblastoma. We conclude that Dicer1 functions as a haploinsufficient tumor suppressor. This finding has implications for cancer etiology and cancer therapy.
Keywords
LUNG-CANCER, STEM-CELLS, MOUSE RETINA, N-MYC GENE, TUMOR-SUPPRESSOR GENES, haploinsufficiency, tumor suppressor, retinoblastoma, Dicer, microRNA, RETINOBLASTOMA, EXPRESSION, MICRORNAS, PROLIFERATION, CHX10

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 1.08 MB

Citation

Please use this url to cite or link to this publication:

MLA
Lambertz, Irina et al. “Monoallelic but Not Biallelic Loss of Dicer1 Promotes Tumorigenesis in Vivo.” CELL DEATH AND DIFFERENTIATION 17.4 (2010): 633–641. Print.
APA
Lambertz, I., Nittner, D., Mestdagh, P., Denecker, G., Vandesompele, J., Dyer, M., & Marine, J.-C. (2010). Monoallelic but not biallelic loss of Dicer1 promotes tumorigenesis in vivo. CELL DEATH AND DIFFERENTIATION, 17(4), 633–641.
Chicago author-date
Lambertz, Irina, David Nittner, Pieter Mestdagh, Geertrui Denecker, Jo Vandesompele, MA Dyer, and Jean-Christophe Marine. 2010. “Monoallelic but Not Biallelic Loss of Dicer1 Promotes Tumorigenesis in Vivo.” Cell Death and Differentiation 17 (4): 633–641.
Chicago author-date (all authors)
Lambertz, Irina, David Nittner, Pieter Mestdagh, Geertrui Denecker, Jo Vandesompele, MA Dyer, and Jean-Christophe Marine. 2010. “Monoallelic but Not Biallelic Loss of Dicer1 Promotes Tumorigenesis in Vivo.” Cell Death and Differentiation 17 (4): 633–641.
Vancouver
1.
Lambertz I, Nittner D, Mestdagh P, Denecker G, Vandesompele J, Dyer M, et al. Monoallelic but not biallelic loss of Dicer1 promotes tumorigenesis in vivo. CELL DEATH AND DIFFERENTIATION. 2010;17(4):633–41.
IEEE
[1]
I. Lambertz et al., “Monoallelic but not biallelic loss of Dicer1 promotes tumorigenesis in vivo,” CELL DEATH AND DIFFERENTIATION, vol. 17, no. 4, pp. 633–641, 2010.
@article{833552,
  abstract     = {Human tumors are characterized by widespread reduction in microRNA (miRNA) expression, although it is unclear how such changes come about and whether they have an etiological role in the disease. Importantly, miRNA knockdown has been shown to enhance the tumorigenic potential of human lung adenocarcinoma cells. A defect in miRNA processing is one possible mechanism for global downregulation. To explore this possibility in more detail in vivo, we have manipulated Dicer1 gene dosage in a mouse model of retinoblastoma. We show that although monoallelic loss of Dicer1 does not affect normal retinal development, it dramatically accelerates tumor formation on a retinoblastoma-sensitized background. Importantly, these tumors retain one wild-type Dicer1 allele and exhibit only a partial decrease in miRNA processing. Accordingly, in silico analysis of human cancer genome data reveals frequent hemizygous, but not homozygous, deletions of DICER1. Strikingly, complete loss of Dicer1 function in mice did not accelerate retinoblastoma formation. miRNA profiling of these tumors identified members of the let-7 and miR-34 families as candidate tumor suppressors in retinoblastoma. We conclude that Dicer1 functions as a haploinsufficient tumor suppressor. This finding has implications for cancer etiology and cancer therapy.},
  author       = {Lambertz, Irina and Nittner, David and Mestdagh, Pieter and Denecker, Geertrui and Vandesompele, Jo and Dyer, MA and Marine, Jean-Christophe},
  issn         = {1350-9047},
  journal      = {CELL DEATH AND DIFFERENTIATION},
  keywords     = {LUNG-CANCER,STEM-CELLS,MOUSE RETINA,N-MYC GENE,TUMOR-SUPPRESSOR GENES,haploinsufficiency,tumor suppressor,retinoblastoma,Dicer,microRNA,RETINOBLASTOMA,EXPRESSION,MICRORNAS,PROLIFERATION,CHX10},
  language     = {eng},
  number       = {4},
  pages        = {633--641},
  title        = {Monoallelic but not biallelic loss of Dicer1 promotes tumorigenesis in vivo},
  url          = {http://dx.doi.org/10.1038/cdd.2009.202},
  volume       = {17},
  year         = {2010},
}

Altmetric
View in Altmetric
Web of Science
Times cited: