Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation.
MicroRNAs (miRNAs) are approximately 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.
Mayr
Christine
C
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.
Hemann
Michael T
MT
Bartel
David P
DP
D020413:3' Untranslated Regions; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D025743:HMGA2 Protein / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D041681:NIH 3T3 Cells; D009374:Neoplasms, Experimental / Q000209:etiology / Q000235:genetics; D009857:Oncogenes; D014162:Transfection; D014178:Translocation, Genetic
D020413:3' Untranslated Regions; D025743:HMGA2 Protein; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human