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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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Nucleic Acids Res. 37, D98-D104
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Coordinated Regulation of Cell Cycle Transcripts by p53-Inducible microRNAs, miR-192 and miR-215.
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Cancer Res. 68, 10105-10112
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MicroRNA Microarray Identifies Let-7i as a Novel Biomarker and Therapeutic Target in Human Epithelial Ovarian Cancer.
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Cancer Res. 68, 10307-10314
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In-depth characterization of the microRNA transcriptome in a leukemia progression model.
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