期刊
MOLECULAR THERAPY-ONCOLYTICS
卷 19, 期 -, 页码 283-293出版社
CELL PRESS
DOI: 10.1016/j.omto.2020.10.008
关键词
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资金
- National Natural Science Foundation of China [81960477, 81760478, 81602315, 81660424, 81560468]
- China Postdoctoral Science Foundation [2017M623295XB]
- Natural Science Foundation of Guangxi [1598012-42, 2016GXNSFBA380139]
- Guangxi Medical University Training Program for Distinguished Young Scholars
Emerging evidence has shown the role of mesenchymal stem cell-derived exosome (MSC-exo) in inducing resistance of cancer cells to chemotherapy. However, it remains unclear whether the change of MSC-exo in response to chemotherapy also contributes to chemoresistance. In this study, we investigated the effect of a standard-of-care chemotherapeutic agent, doxorubicin (Dox), on MSC-exo and its contribution to the development of Dox resistance in breast cancer cells (BCs). We found that the exosome secreted by Dox-treated MSCs (Dt-MSC-exo) induced a higher degree of Dox resistance in BCs when compared with non-treated MSC-exo. By analysis of the MSC-exo-induced transcriptome change in BCs, we identified S100A6, a chemoresistant gene, as a top-ranked gene induced by MSC-exo in BCs, which was further enhanced by Dt-MSCexo. Furthermore, we found that Dox induced the expression of miR-21-5p in MSCs and MSC-exo, which was required for the expression of S100A6 in BCs. Importantly, silencing of miR-21-5p expression in MSCs and MSC-exo abolished the resistance of BCs to Dox, indicating an exosomal miR-21-5p-regulated S100A6 in chemoresistance. Our study thus uncovered a novel mechanistic insight into the role of MSC-secreted exosome in the development of chemoresistance in the tumor microenvironment.
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