期刊
ONCOLOGY REPORTS
卷 33, 期 5, 页码 2504-2512出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2015.3866
关键词
miR-141; docetaxel; drug resistance; breast cancer; EIF4E
类别
资金
- Shandong Natural Science Foundation [Y2006C23]
Resistance to docetaxel, a chemotherapy drug for breast cancer (BC) treatment, occurs in similar to 50% of patients, and the underlying molecular mechanisms of drug resistance are not fully understood. Gene regulation through miR-141 has been proven to play an important role in cancer drug resistance. The present study investigated the role of miR-141 expression in BC cells of acquired docetaxel resistance. Inhibition of miR-141 enhanced the response to docetaxel in docetaxel-resistant cells. (MCF-7/DTX and MDA-MB-231/DTX, respectively), whereas overexpression of miR-141 confered resistance in docetaxel-sensitive cells (MCF-7 and MDA-MB-231, respectively). By directly targeting the eukaryotic translation initiation factor 4E (EIF4E) mRNA, miR-141 acts on genes that are necessary for drug induced apoptosis rendering the cells drug resistant. Modulation of miR-141 expression was correlated with EIF4E expression changes and a direct interaction of miR-141 with EIF4E was shown by a luciferase assay. Thus, the present study is the first to show an increased expression of miR-141 in an acquired model of docetaxel resistance in BC. This serves as a mechanism of acquired docetaxel resistance in BC cells, possibly through direct interactions with EIF4E, therefore presenting a potential therapeutic target for the treatment of docetaxel resistant BC.
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