Xiaolei Hu1, Pingmei Huang1, Jie Wang2, Wan He3, Pan Zhao4, Guangyu Yao1, Changsheng Ye1. 1. Breast Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. 2. Department of Clinical Nutrition, 458 Hospital of PLA, Guangzhou 510602, China. 3. Department of Oncology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen 518020, China. 4. Clinical Medical Research Center, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen 518020, China.
Abstract
OBJECTIVE: To investigate the role of miR- 433 in chemoresistance to docetaxel in breast cancer cells. METHODS: A docetaxel-resistant MCF-7 breast cancer cell line (MCF-7/DOX) was established by exposure of parental MCF-7 cells to progressively increased docetaxel concentrations. The functional role of miR-433 was investigated by assessing the changes in viability and apoptosis of the cells transfected with a miR-433 inhibitor or a miR-433 mimics. The downstream targets of miR- 433 were determined by bioinformatics analysis, cell transfection and luciferase reporter assay. RESULTS: Quantitative real-time PCR analysis showed that miR- 433 was down-regulated in MCF-7/DOX cells. Transfection of the cells with the miR-433 inhibitor obviously enhanced chemoresistance to docetaxel and attenuated cell apoptosis in MCF-7 cells; miR-433 overexpression significantly increased the sensitivity to docetaxel and promoted apoptosis in MCF- 7/DOX cells. Luciferase reporter assay showed that the down-regulation miR-433 expression was associated with significantly increased expressions of Notch1 at both mRNA and protein levels in MCF-7 cells. Compared with the control cells, McF-7/DOX cells transfected with miR-433 mimics exhibited significantly decreased mRNA and protein expressions of Notch1. CONCLUSIONS: miR-433 may reverse chemoresistance to docetaxel by targeting Notch1 in breast cancer cells.
OBJECTIVE: To investigate the role of miR- 433 in chemoresistance to docetaxel in breast cancer cells. METHODS: A docetaxel-resistant MCF-7 breast cancer cell line (MCF-7/DOX) was established by exposure of parental MCF-7 cells to progressively increased docetaxel concentrations. The functional role of miR-433 was investigated by assessing the changes in viability and apoptosis of the cells transfected with a miR-433 inhibitor or a miR-433 mimics. The downstream targets of miR- 433 were determined by bioinformatics analysis, cell transfection and luciferase reporter assay. RESULTS: Quantitative real-time PCR analysis showed that miR- 433 was down-regulated in MCF-7/DOX cells. Transfection of the cells with the miR-433 inhibitor obviously enhanced chemoresistance to docetaxel and attenuated cell apoptosis in MCF-7 cells; miR-433 overexpression significantly increased the sensitivity to docetaxel and promoted apoptosis in MCF- 7/DOX cells. Luciferase reporter assay showed that the down-regulation miR-433 expression was associated with significantly increased expressions of Notch1 at both mRNA and protein levels in MCF-7 cells. Compared with the control cells, McF-7/DOX cells transfected with miR-433 mimics exhibited significantly decreased mRNA and protein expressions of Notch1. CONCLUSIONS:miR-433 may reverse chemoresistance to docetaxel by targeting Notch1 in breast cancer cells.
Entities:
Keywords:
MCF-7; Notch1; breast cancer; chemoresistance; docetaxel; miR-433
Authors: X Xu; Y Zhu; Z Liang; S Li; X Xu; X Wang; J Wu; Z Hu; S Meng; B Liu; J Qin; L Xie; X Zheng Journal: Cell Death Dis Date: 2016-02-04 Impact factor: 8.469