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A Genetic Screen Implicates miRNA-372 and miRNA-373 as Oncogenes in Testicular Germ Cell Tumors

  • P. Mathijs Voorhoeve
  • Carlos le Sage
  • Mariette Schrier
  • Ad J. M. Gillis
  • Hans Stoop
  • Remco Nagel
  • Ying-Poi Liu
  • Josyanne van Duijse
  • Jarno Drost
  • Alexander Griekspoor
  • Eitan Zlotorynski
  • Norikazu Yabuta
  • Gabriella De Vita
  • Hiroshi Nojima
  • Leendert H. J. Looijenga
  • Reuven Agami
Part of the Advances In Experimental Medicine And Biology book series (AEMB, volume 604)

Endogenous small RNAs (miRNAs) regulate gene expression by mechanisms conserved across metazoans. While the number of verified human miRNAs is still expanding, only few have been functionally annotated. To perform genetic screens for novel functions of miRNAs, we developed a library of vectors expressing the majority of cloned human miRNAs and created corresponding DNA barcode arrays. In a screen for miRNAs that cooperate with oncogenes in cellular transformation, we identified miR-372 and miR-373, each permitting proliferation and tumorigenesis of primary human cells that harbor both oncogenic RAS and active wild-type p53. These miRNAs neutralize p53-mediated CDK inhibition, possibly through direct inhibition of the expression of the tumorsuppressor LATS2. We provide evidence that these miRNAs are potential novel oncogenes participating in the development of human testicular germ cell tumors by numbing the p53 pathway, thus allowing tumorigenic growth in the presence of wild-type p53.

Keywords

Genetic Screen RNase Protection Assay microRNA Target Primary Human Cell Oncogenic Stress 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer 2007

Authors and Affiliations

  • P. Mathijs Voorhoeve
    • 1
  • Carlos le Sage
    • 1
  • Mariette Schrier
    • 1
  • Ad J. M. Gillis
    • 2
  • Hans Stoop
    • 2
  • Remco Nagel
    • 1
  • Ying-Poi Liu
    • 1
  • Josyanne van Duijse
    • 1
  • Jarno Drost
    • 1
  • Alexander Griekspoor
    • 1
  • Eitan Zlotorynski
    • 1
  • Norikazu Yabuta
    • 3
  • Gabriella De Vita
    • 4
  • Hiroshi Nojima
    • 3
  • Leendert H. J. Looijenga
    • 2
  • Reuven Agami
    • 1
  1. 1.Division of Tumour BiologyThe Netherlands Cancer InstituteThe Netherlands
  2. 2.Department of Pathology Erasmus University Medical Center RotterdamJosephine Nefkens InstituteThe Netherlands
  3. 3.Department of Molecular GeneticsOsaka UniversityJapan
  4. 4.Dipartimento di Biologia e Patologia Cellulare e MolecolareUniversitá Federico IIItaly

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