title: miR-100 suppresses IGF2 and inhibits breast tumorigenesis by interfering with proliferation and survival signaling.
abstract: Dysregulation of micro RNAs is crucially implicated in tumorigenesis. We detected downregulation of miR-100 in breast cancer cells, leading to an upregulation of the proliferation- and survival-promoting oncogene insulin-like growth factor (IGF) 2. Stable overexpression of miR-100 strongly reduced IGF2 expression and inhibited tumor growth. In invasive human breast tumors, miR-100 was reduced about fourfold as compared with benign patient samples, whereas IGF2 was strongly enhanced. MiR-100 has also been shown to suppress other proteins of the IGF/mammalian target of rapamycin (mTOR) signaling cascade in different human tumors. Our results reveal miR-100 as a context-dependent master regulator of the IGF/mTOR pathway and a potential target for therapeutic approaches.
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria. christoph.gebeshuber@meduniwien.ac.at
authors.forename: C A
authors.initials: CA
authors.lastname: Gebeshuber
authors.forename: J
authors.initials: J
authors.lastname: Martinez
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: C035170:IGF2 protein, human; C544266:MIRN100 microRNA, human; D035683:MicroRNAs; D007335:Insulin-Like Growth Factor II; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases