Abstract |
The emergence of drug resistance is still a daunting challenge for the effective therapy of cancer patients. miRNAs have been elucidated as an important regulator in chemoresistance of anti- cancer drugs. miR-381 is found to exert tumor-suppressive effect in breast cancer. However, its role in modulating the sensitivity of doxorubicin (DOX) remains unknown. In this study, we found that miR-381 expression was down-regulated in DOX-resistant breast cancer cells. miR-381 overexpression increased DOX sensitivity and enhanced DOX-induced apoptosis in breast cancer cells. Moreover, miR-381 could directly target FYN to suppress its expression. Additionally, FYN knockdown displayed similar effect on DOX sensitivity as miR-381 up-regulation. Furthermore, FYN overexpression partly reversed miR-381-induced sensitivity to DOX. Finally, enforced expression of miR-381 also improved DOX sensitivity of breast cancer cells in vivo. In summary, miR-381 inactivated MAPK signaling by down-regulating FYN, thereby promoting the chemosensitization of breast cancer cells to DOX. Therefore, miR-381/FYN/MAPK pathway may be applied as a novel target to overcome DOX resistance in breast cancer patients.
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Authors | Hailong Mi, Xiaochun Wang, Fang Wang, Lin Li, Mingzhi Zhu, Nan Wang, Youyi Xiong, Yuanting Gu |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 839
Pg. 66-75
(Nov 15 2018)
ISSN: 1879-0712 [Electronic] Netherlands |
PMID | 30266665
(Publication Type: Journal Article)
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Copyright | Copyright © 2018 Elsevier B.V. All rights reserved. |
Chemical References |
- MIRN381 microRNA, human
- MicroRNAs
- Doxorubicin
- Proto-Oncogene Proteins c-fyn
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Topics |
- Animals
- Apoptosis
(drug effects, genetics)
- Base Sequence
- Breast Neoplasms
(pathology)
- Down-Regulation
(drug effects, genetics)
- Doxorubicin
(pharmacology)
- Drug Resistance, Neoplasm
(drug effects, genetics)
- Humans
- MAP Kinase Signaling System
(drug effects, genetics)
- MCF-7 Cells
- Male
- Mice
- MicroRNAs
(genetics)
- Proto-Oncogene Proteins c-fyn
(genetics)
- Xenograft Model Antitumor Assays
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