miR-100 suppresses IGF2 and inhibits breast tumorigenesis by interfering with proliferation and survival signaling

• DOI: 10.1038/onc.2012.372
• Publication Date: 2012-08-27T13:23:10Z
• Authors: C A Gebeshuber; J Martinez
• Keywords: 0303 health sciences; Cell Survival; TOR Serine-Threonine Kinases; Blotting, Western; Breast Neoplasms; Blotting, Northern; Polymerase Chain Reaction; Gene Expression Regulation, Neoplastic; Mice; MicroRNAs; 03 medical and health sciences; Cell Transformation, Neoplastic; Insulin-Like Growth Factor II; Cell Line, Tumor; Mutagenesis, Site-Directed; Animals; Humans; Female; Cell Proliferation; Signal Transduction

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.