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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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