Abstract 3062: miR-671-5p promotes epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer

microRNA (miRNA) dysfunction is associated with a variety of human diseases including cancer. Our previous study showed that miR-671-5p was deregulated during breast cancer progression. We aim to decipher the functional mechanism of miR-671-5p in breast cancer. We found that expression of miR-671-5p was decreased significantly in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) compared to normal and atypical ductal hyperplasia (ADH) in the microdissected formalin-fixed, paraffin-embedded (FFPE) tissues. Forkhead Box M1 (FOXM1), as an oncogenic transcription factor, was predicted as one of the direct targets of miR-671-5p, which was subsequently confirmed by luciferase assays. Forced expression of miR-671-5p in breast cancer cell lines downregulated FOXM1 expression, and attenuated the proliferation and invasion in breast cancer cell lines. Notably, overexpression of miR-671-5p resulted in a shift from epithelial-to-mesenchymal transition (EMT) to mesenchymal-to-epithelial transition (MET) phenotypes in MDA-MB-231 breast cancer cells and induced S-phase arrest. Moreover, miR-671-5p sensitized breast cancer cells to cisplatin, 5-fluorouracil (5-FU) and epirubicin exposure. Host cell reactivation (HCR) assays showed that miR-671-5p reduces DNA repair capability in post-drug exposed breast cancer cells. These data indicates that miR-671-5p functions as a tumor suppressor miRNA by directly targeting FOXM1 in breast cancer. Hence, miR-671-5p may serve as a novel therapeutic target for breast cancer management. Citation Format: Xiaohui Tan, Yebo Fu, Liang Chen, Shejuan An, Woojin Lee, Yinglei Lai, Katayoon Rezaei, Sana Tabbara, Christine B. Teal, Yan-gao Man, Robert Siegel, Rachel F. Brem, Sidney W. Fu. miR-671-5p promotes epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3062. doi:10.1158/1538-7445.AM2015-3062