Abstract 5031: miR-21 targets TGF-β Pathway in breast cancer

MicroRNAs (miRNAs) are endogenous non-coding RNAs (∼22 nt), which regulate the stability and translation of coding mRNAs. miRNA dysregulation is observed in a variety of cancers, including breast cancer. Our previous studies, by miRNA expression profiling using archived FFPE tissues, identified a set of miRNAs that are differentially expressed during breast cancer progression. Using ANOVA test, we identified 8 clusters of miRNAs, which discrete the normal and disease lesions, such as ADH, DCIS and IDC. miR-21 has been well documented as an oncogene, while miR-200c/b are reported as biomarkers for primary hepatocellular carcinoma, and miR-200c as an independent prognostic factor in pancreatic cancer. Our study shows that miR-21 consistently expresses high level in pre-cancerous lesions, i.e. ADH and DCIS, which indicates that miR-21 plays an important role in breast cancer initiation and progression. However, the exact mechanism is not clear. To test the effects of miR-21 inhibition in both ER+ and ER- breast cancer cells, we transfected anti-miR-21 oligos and scrambled oligo mocks into human breast cancer cells, MCF-7 (ER+) and Hs578T (ER-). We observed a significantly increased expression of MSH2 and SMAD7, when miR-21 was knocked down by 60%-80%. Both MSH2 and SMAD7 are key players in TGF-β signaling pathway, which is well known for its anti-mitogenic function during tumor initiation. These findings help establish miR-21 as an important oncogene that targets a network of TGF-β in breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5031. doi:1538-7445.AM2012-5031