miR-381 induces sensitivity of breast cancer cells to doxorubicin by inactivation of MAPK signaling via FYN
| Autor: | Youyi Xiong, Hailong Mi, Nan Wang, Fang Wang, Lin Li, Mingzhi Zhu, Xiaochun Wang, Yuanting Gu |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine MAPK/ERK pathway MAP Kinase Signaling System Down-Regulation Apoptosis Breast Neoplasms Proto-Oncogene Proteins c-fyn Mice 03 medical and health sciences 0302 clinical medicine Breast cancer FYN microRNA polycyclic compounds medicine Animals Humans Doxorubicin Pharmacology Gene knockdown Base Sequence Chemistry Cancer medicine.disease Xenograft Model Antitumor Assays carbohydrates (lipids) MicroRNAs 030104 developmental biology Drug Resistance Neoplasm 030220 oncology & carcinogenesis MCF-7 Cells Cancer research medicine.drug |
| Zdroj: | European Journal of Pharmacology. 839:66-75 |
| ISSN: | 0014-2999 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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