Abstract P4-07-07: Reduced expression of miR-200c-3p contributes to cell migration and invasion in paclitaxel-resistant breast cancer cell

Abstract

Abstract Background: miRNAs are a class of small noncoding RNA molecules that regulate gene expression by degradation of target mRNAs or inhibition of translation. Metastasis is one of the major problems that give obstacles to improve the clinical outcome of breast cancer. However, the underlying molecular mechanism of breast cancer metastasis remains largely unclear. Emerging studies have demonstrated that miRNAs play an important part in tumor invasion and metastasis. In the present study, we aimed to investigate the role and mechanism of miR-200c-3p in regulating the migration and invasion of paclitaxel-resistant breast cancer cells, and identify potential targets for breast cancer treatments. Material and methods: Paclitaxel-resistant breast cancer cell line MCF-7/Tax was established by stepwise selection in increasing concentration of paclitaxel. The 50% inhibitory concentration and cell viability were measured by the MTT assay. The expression level of miR-200c-3p in MCF-7/Tax and the parental MCF-7 cells was assessed by quantitative real-time RT-PCR. Gain-of-function and loss-of-function study on cell migration and invasion abilities were carried out by transfection of miR-200c-3p mimics or inhibitors respectively. The molecular target of miR-200c-3p was verified by dual-luciferase reporter assay. Results: Paclitaxel-resistant breast cancer cell line MCF-7/Tax was established. Compared with parental MCF-7 cells, expression of miR-200c-3p determined by real-time RT-PCR was significantly down-regulated in paclitaxel-resistant MCF-7/Tax cells. The ability of migration and invasion of paclitaxel-resistant MCF-7/Tax cells was obviously increased as compared to parental MCF-7 cells. In addition, we found that up-regulation of miR-200c-3p expression inhibited the migration and invasion of MCF-7/Tax cells, while down-regulation of miR-200c-3p expression increased the migration and invasion of MCF-7/Tax cells. Dual-luciferase reporter assay demonstrated that SOX2 was one of the direct targets of miR-200c-3p in breast cancer. Conclusions: Our results indicate that reduced expression of miR-200c-3p plays a crucial role in cell migration and invasion of paclitaxel-resistant breast cancer cell, and miR-200c-3p may suppress the cell migration and invasion possibly partially through SOX2. Our findings suggest that miR-200c-3p may serve as a promising therapeutic target for breast cancer metastasis. Keywords miRNA · Breast cancer ·Invasion Acknowledgments: The project supported by the grant of the Natural Science Foundation of Zhejiang Province (No.LQ13H160016), and the Medical Sciences and Technology of Zhejiang Province (No.2013KYA026, No.2015DTA004). Citation Format: Wang X, Chen J, Chen Z, Huang J, Ye W. Reduced expression of miR-200c-3p contributes to cell migration and invasion in paclitaxel-resistant breast cancer cell [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-07-07.