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Science 315 (5818): 1576-1579

Copyright © 2007 by the American Association for the Advancement of Science

Disrupting the Pairing Between let-7 and Hmga2 Enhances Oncogenic Transformation

Christine Mayr,1 Michael T. Hemann,2 David P. Bartel1*

Abstract: MicroRNAs (miRNAs) are ~22-nucleotide RNAs that can pair to sites within messenger RNAs to specify posttranscriptional repression of these messages. Aberrant miRNA expression can contribute to tumorigenesis, but which of the many miRNA-target relationships are relevant to this process has been unclear. Here, we report that chromosomal translocations previously associated with human tumors disrupt repression of High Mobility Group A2 (Hmga2) by let-7 miRNA. This disrupted repression promotes anchorage-independent growth, a characteristic of oncogenic transformation. Thus, losing miRNA-directed repression of an oncogene provides a mechanism for tumorigenesis, and disrupting a single miRNA-target interaction can produce an observable phenotype in mammalian cells.

1 Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, and Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
2 Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

* To whom correspondence should be addressed. E-mail: dbartel{at}wi.mit.edu

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   Abstract »    Full Text »    PDF »
MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators.
G. Gabriely, T. Wurdinger, S. Kesari, C. C. Esau, J. Burchard, P. S. Linsley, and A. M. Krichevsky (2008)
Mol. Cell. Biol. 28, 5369-5380
   Abstract »    Full Text »    PDF »
Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing.
M. A. Newman, J. M. Thomson, and S. M. Hammond (2008)
RNA 14, 1539-1549
   Abstract »    Full Text »    PDF »
Determinants of MicroRNA Processing Inhibition by the Developmentally Regulated RNA-binding Protein Lin28.
E. Piskounova, S. R. Viswanathan, M. Janas, R. J. LaPierre, G. Q. Daley, P. Sliz, and R. I. Gregory (2008)
J. Biol. Chem. 283, 21310-21314
   Abstract »    Full Text »    PDF »
MicroRNA miR-199a* Regulates the MET Proto-oncogene and the Downstream Extracellular Signal-regulated Kinase 2 (ERK2).
S. Kim, U. J. Lee, M. N. Kim, E.-J. Lee, J. Y. Kim, M. Y. Lee, S. Choung, Y. J. Kim, and Y.-C. Choi (2008)
J. Biol. Chem. 283, 18158-18166
   Abstract »    Full Text »    PDF »
Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer.
L. Zhang, S. Volinia, T. Bonome, G. A. Calin, J. Greshock, N. Yang, C.-G. Liu, A. Giannakakis, P. Alexiou, K. Hasegawa, et al. (2008)
PNAS 105, 7004-7009
   Abstract »    Full Text »    PDF »
Identification of Let-7-Regulated Oncofetal Genes.
B. Boyerinas, S.-M. Park, N. Shomron, M. M. Hedegaard, J. Vinther, J. S. Andersen, C. Feig, J. Xu, C. B. Burge, and M. E. Peter (2008)
Cancer Res. 68, 2587-2591
   Abstract »    Full Text »    PDF »

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