TY - JOUR T1 - miR-200c suppresses stemness and increases cellular sensitivity to trastuzumab in HER2+ breast cancer JF - bioRxiv DO - 10.1101/130682 SP - 130682 AU - Cailu Song AU - Jin Wang AU - Hua Wang AU - Peng Liu AU - Longzhong Liu AU - Lu Yang AU - Hailin Tang AU - Xiaoming Xie Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/04/25/130682.abstract N2 - Resistance to trastuzumab remains a major obstacle in HER2-overexpressing breast cancer treatment. miR-200c is important for many functions in cancer stem cells (CSCs), including tumor recurrence, metastasis and resistance. We hypothesized that miR-200c contributes to trastuzumab resistance and stemness maintenance in HER2-overexpressing breast cancer. In this study, we used HER2-positive SKBR3, HER2-negative MCF-7, and their CD44+CD24- phenotype mammospheres SKBR3-S and MCF-7-S to verify. Our results demonstrated that miR-200c was weakly expressed in breast cancer cell lines and cell line stem cells. Overexpression of miR-200c resulted in a significant reduction in the number of tumor spheres formed and the population of CD44+CD24- phenotype mammospheres in SKBR3-S. Combining miR-200c with trastuzumab can significantly reduce proliferation and increase apoptosis of SKBR3 and SKBR3-S. Overexpression of miR-200c also eliminated its downstream target genes. These genes were highly expressed and positively related in breast cancer patients. Overexpression of miR-200c also improved the malignant progression of SKBR3-S and SKBR3 in vivo. miR-200c plays an important role in the maintenance of the CSC-like phenotype and increases drug sensitivity to trastuzumab in HER2+ cells and stem cells.Summary statement miRNAs are critical in stemness maintenance and drug resistance. These data link maintenance of the stemness-related phenotype and the sensitivity of HER2+ breast cancer to miR-200c in response to trastuzumab. ER -