title: MiR-181a enhances drug sensitivity in mitoxantone-resistant breast cancer cells by targeting breast cancer resistance protein (BCRP/ABCG2).
abstract: Breast cancer resistance protein (BCRP)/ATP-binding cassette subfamily G member 2 (ABCG2) mediates multidrug resistance (MDR) in breast cancers. In this study, we aimed to investigate the role of microRNAs in regulation of BCRP expression and BCRP-mediated drug resistance in breast cancer cells. Microarray analysis was performed to determine the differential expression patterns of miRNAs that target BCRP between the MX-resistant breast cancer cell line MCF-7/MX and its parental MX-sensitive cell line MCF-7. MiR-181a was found to be the most significantly down-regulated miRNA in MCF-7/MX cells. Luciferase activity assay showed that miR-181a mimics inhibited BCRP expression by targeting the 3' untranslated region (UTR) of the BCRP mRNA. Overexpression of miR-181a down-regulated BCRP expression, and sensitized MX-resistant MCF-7/MX cells to MX. In a nude mouse xenograft model, intratumoral injection of miR-181a mimics inhibited BCRP expression, and enhanced the antitumor activity of MX. In addition, miR-181a inhibitors up-regulated BCRP expression, and rendered MX-sensitive MCF-7 cells resistant to MX. These findings suggest that miR-181a regulates BCRP expression via binding to the 3'-UTR of BCRP mRNA. MiR-181a is critical for regulation of BCRP-mediated resistance to MX. MiR-181a may be a potential target for preventing and reversing drug resistance in breast cancer.
authors.affiliation: Department of Pharmacology, China Medical University, North 2nd Road 92, Heping Ward, Shenyang 110001, Liaoning, China.
authors.forename: Xuyang
authors.initials: X
authors.lastname: Jiao
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.forename: Mengtao
authors.initials: M
authors.lastname: Ma
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Bai
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Yan
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Qiuchen
authors.initials: Q
authors.lastname: Chen
authors.forename: Xinnan
authors.initials: X
authors.lastname: Zhao
authors.forename: Mingyi
authors.initials: M
authors.lastname: Zhou
authors.forename: Zeshi
authors.initials: Z
authors.lastname: Cui
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zheng
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
authors.forename: Minjie
authors.initials: M
authors.lastname: Wei
mesh_terms: D020413:3' Untranslated Regions; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008942:Mitoxantrone / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D008942:Mitoxantrone