title: Down-regulation of microRNA-200c is associated with drug resistance in human breast cancer.
abstract: Drug resistance remains a major clinical obstacle to successful treatment in breast cancer patients, and the evidence of microRNAs involvement in cancer drug resistance has been emerging recently. However, the role of microRNA-200c (miR-200c) in modulating chemoresistance of breast cancer remains largely unexplored. Here, we investigated the miR-200c expression in tumor specimens obtained from thirty-nine breast cancer patients who received neoadjuvent chemotherapy by quantitative real-time PCR. Down-regulated miR-200c was observed in non-responders as compared to responders. In addition, miR-200c expression was observed to be down-regulated over 800-fold in human breast cancer cells resistant to doxorubicin MCF-7/ADR as compared to the parental MCF-7 cells. Up-regulation of miR-200c with transfection of miR-200c mimics in breast cancer cells could enhance the chemosensitivity to epirubicin and reduce expression of multidrug resistance 1 mRNA and P-glycoprotein. Moreover, our study demonstrated that restoration of miR-200c in MCF-7/ADR cells could increase intracellular doxorubicin accumulation determined by flow cytometry. Taken together, our findings suggest that miR-200c may act as a promising therapeutic target for improvement of responsiveness to chemotherapy in breast cancer.
authors.affiliation: Department of Surgical Oncology, Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, School of Medicine Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
authors.forename: Junqing
authors.initials: J
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.forename: Hongke
authors.initials: H
authors.lastname: Cai
authors.forename: Haifei
authors.initials: H
authors.lastname: He
authors.forename: Yongchuan
authors.initials: Y
authors.lastname: Deng
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
chemical_list: C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012333:RNA, Messenger
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