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Disrupting the Pairing Between let-7 and Hmga2 Enhances Oncogenic Transformation
Christine Mayr,1Michael T. Hemann,2David P. Bartel1*
MicroRNAs (miRNAs) are 22-nucleotide RNAs that can pair to siteswithin messenger RNAs to specify posttranscriptional repressionof these messages. Aberrant miRNA expression can contributeto tumorigenesis, but which of the many miRNA-target relationshipsare relevant to this process has been unclear. Here, we reportthat chromosomal translocations previously associated with humantumors disrupt repression of High Mobility Group A2 (Hmga2)by let-7 miRNA. This disrupted repression promotes anchorage-independentgrowth, a characteristic of oncogenic transformation. Thus,losing miRNA-directed repression of an oncogene provides a mechanismfor tumorigenesis, and disrupting a single miRNA-target interactioncan 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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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. 
