| Autor: |
Xing, Yang, Qian, Hu, Lan-Xin, Hu, Xiao-Rong, Lin, Jie-Qiong, Liu, Xiao, Lin, Xiao-Xiao, Dinglin, Jia-Yi, Zeng, Hai, Hu, Man-Li, Luo, He-Rui, Yao |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Discovery medicine. 24(131) |
| ISSN: |
1944-7930 |
| Popis: |
Chemotherapy is a cornerstone treatment for early and advanced stage breast cancer patients. However, resistance to chemotherapy remains a major obstacle, resulting in disease relapse and progression. Emerging studies demonstrated that miRNAs regulate chemotherapy-induced epithelial-mesenchymal transition (EMT) and drug resistance, but the underlying mechanisms remain unclear. Here we established a doxorubicin-resistant breast cancer cell line MCF-7/Adr, and found these cells exhibited an EMT phenotype featured by a fibroblast-like morphology, increased the capacity of migration and invasion, and underwent the changes of molecular markers of EMT including E-cadherin, N-cadherin, and vimentin. We then compared the miRNA expression profiles between MCF-7/Adr and parental MCF-7 by miRNA microarray, and identified miR-200b as the most dramatically down-regulated miRNA. Overexpression of miR-200b in chemo-resistant cells reversed the EMT phenotype and increased sensitivity to doxorubicin. Inhibition of miR-200b in parental cells induced EMT and resistance to doxorubicin. Furthermore, we characterized the target gene of miR-200b, and showed that overexpression of miR-200b down-regulated FN1 expression and the luciferase activity. Compared with the parental cells, FN1 was significantly elevated in MCF-7/Adr cells. Knockdown of FN1 reversed mesenchymal morphology, inhibited cell migration and invasion, and sensitized cells to doxorubicin. Our data suggest that miR-200b regulates EMT of chemo-resistant breast cancer cells by targeting FN1. miR-200b-based therapy may be an effective strategy in treating advanced breast cancer patients. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
