title: 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.
authors: Department of Oncology, Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, P.R. China.
authors: Ya-Sai
authors: YS
authors: Yao
authors: Department of Oncology, Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, P.R. China.
authors: Wen-Sheng
authors: WS
authors: Qiu
authors: Central Laboratory, Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, P.R. China.
authors: Ru-Yong
authors: RY
authors: Yao
authors: Central Laboratory, Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, P.R. China.
authors: Qian
authors: Q
authors: Zhang
authors: Central Laboratory, Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, P.R. China.
authors: Li-Kun
authors: LK
authors: Zhuang
authors: Department of Oncology, Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, P.R. China.
authors: Fei
authors: F
authors: Zhou
authors: Department of Oncology, Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, P.R. China.
authors: Li-Bin
authors: LB
authors: Sun
authors: Department of Oncology, Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, P.R. China.
authors: Lu
authors: L
authors: Yue
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics*; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D043823:Taxoids / Q000494:pharmacology*
chemical_list: C411571:EIF4ENIF1 protein, human; C533895:MIRN141 microRNA, human; D035683:MicroRNAs; D029543:Nucleocytoplasmic Transport Proteins; D012333:RNA, Messenger; D043823:Taxoids; D000077143:Docetaxel