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

Abstract

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 docetaxelsensitive 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.

Taxotere-induced elevated expression of IL8 in carcinoma-associated fibroblasts of breast invasive ductal cancer

“…Drug resistance has severely restricted the application of chemotherapy and neoadjuvant chemotherapy, resulting in treatment failure. Therefore, various researchers have focused on the mechanism of chemotherapy resistance in breast cancer (11)(12)(13). Emerging evidences has indicated that the tumor microenvironment serves an important role in carcinogenesis and development, which has also been identified to participate in therapeutic resistance (14)(15)(16).…”

Mechanisms of breast cancer resistance to anthracyclines or taxanes

“…3). These MDA-MB-231/Taxol cells also present increased expression of miR-141 [46], which was shown to regulate expression of eukaryotic translation initiation factor 4E, which was involved in breast tumor cell cycle progression (Fig. 3).…”

“…& ,[41][42][43][44][45][46][47][48][49][50][51][52][53][54]. MiRNAs that inhibit P-gp, such as miR-451, miR-320a, and miR-298 are implicated in ADR resistance(Fig.…”

The Network of Non-coding RNAs in Cancer Drug Resistance

“…miR-141 overexpression contributes to acquired chemoresistance, for both in vitro and in vivo models. The initiation factor 4E (EIF4E) mRNA is a target of miR-141, that is involved in drug-induced apoptosis, conferring resistance to docetaxel-sensitive BC cells (155). miR-141 regulates cisplatin sensitivity in non-small lung cancer cells via PDCP4 inhibition and its inhibition increases cisplatin-induced apoptosis (156).…”