miR-141 confers docetaxel chemoresistance of breast cancer cells via regulation of EIF4E expression.

Abstract:

:Resistance to docetaxel, a chemotherapy drug for breast cancer (BC) treatment, occurs in ~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.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Yao YS,Qiu WS,Yao RY,Zhang Q,Zhuang LK,Zhou F,Sun LB,Yue L

doi

10.3892/or.2015.3866

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

2504-12

issue

5

eissn

1021-335X

issn

1791-2431

journal_volume

33

pub_type

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