Involvement of miR-326 in chemotherapy resistance of breast cancer through modulating expression of multidrug resistance-associated protein 1

被引:282
作者
Liang, Zhongxing [1 ]
Wu, Hui [1 ]
Xia, James [2 ]
Li, Yuhua [3 ]
Zhang, Yawei [1 ,4 ]
Huang, Ke [1 ]
Wagar, Nicholas [3 ]
Yoon, Younghyoun [1 ]
Cho, Heidi T. [1 ]
Scala, Stefania [5 ]
Shim, Hyunsuk [1 ,6 ]
机构
[1] Emory Univ, Dept Radiol, Atlanta, GA 30322 USA
[2] GenoSensor Corp, Tempe, AZ 85282 USA
[3] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, CA 30322 USA
[4] Fudan Univ, Canc Inst Hosp, Shanghai 200032, Peoples R China
[5] G Pascale Fdn, Natl Canc Inst, Dept Clin Immunol, I-80131 Naples, Italy
[6] Emory Univ, Winship Canc Inst, Atlanta, CA 30322 USA
关键词
microRNA; Multidrug resistance; MRP-1; Breast cancer; MDR1/P-GLYCOPROTEIN EXPRESSION; MICRORNA PRECURSORS; SYNTHETIC MICRORNA; TUMOR INVASION; TARGETING BCL2; CELLS; METASTASIS; CXCR4; BIOGENESIS; GENES;
D O I
10.1016/j.bcp.2009.10.017
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Multidrug resistance-associated protein (MRP-1/ABCC1) transports a wide range of therapeutic agents and may play a critical role in the development Of multidrug resistance (MDR) in tumor cells. However, the regulation of MRP-1 remains controversial. To explore whether miRNAs are involved in the regulation of MRP-1 expression and modulate the sensitivity of tumor cells to chemotherapeutic agents, we analyzed miRNA expression levels in VP-16-resistant MDR cell line, MCF-7/VP, in comparison with its parent cell line, MCF-7, using a miRNA microarray. MCF-7/VP overexpressed MRP-1 mRNA and protein not MDR-1 and BCRP. miR-326 was downregulated in MCF-7/VP compared to MCF-7. Additionally, miR-326 was downregulated in a panel of advanced breast cancer tissues and consistent reversely with expression levels of MRP-1. Furthermore, the elevated levels of miR-326 in the mimics-transfected VP-16-resistant cell line, MCF-7/VP, downregulated MRP-1 expression and sensitized these cells to VP-16 and doxorubicin. These findings demonstrate for the first time the involvement of miRNAs in multidrug resistance mediated by MRP-1 and suggest that miR-326 may be an efficient agent for preventing and reversing MDR in tumor cells. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:817 / 824
页数:8
相关论文
共 36 条
[1]   Promoter characterization and genomic organization of the human breast cancer resistance protein (ATP-binding cassette transporter G2) gene [J].
Bailey-Dell, KJ ;
Hassel, B ;
Doyle, LA ;
Ross, DD .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 2001, 1520 (03) :234-241
[2]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[3]   Regulation of cellular glutathione modulates nuclear accumulation of daunorubicin in human MCF7 cells overexpressing multidrug resistance associated protein [J].
Benderra, Z ;
Trussardi, A ;
Morjani, H ;
Villa, AM ;
Doglia, SM ;
Manfait, M .
EUROPEAN JOURNAL OF CANCER, 2000, 36 (03) :428-434
[4]   MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells [J].
Chan, JA ;
Krichevsky, AM ;
Kosik, KS .
CANCER RESEARCH, 2005, 65 (14) :6029-6033
[5]   miR-15 and miR-16 induce apoptosis by targeting BCL2 [J].
Cimmino, A ;
Calin, GA ;
Fabbri, M ;
Iorio, MV ;
Ferracin, M ;
Shimizu, M ;
Wojcik, SE ;
Aqeilan, RI ;
Zupo, S ;
Dono, M ;
Rassenti, L ;
Alder, H ;
Volinia, S ;
Liu, CG ;
Kipps, TJ ;
Negrini, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (39) :13944-13949
[6]  
COLE SPC, 1994, CANCER RES, V54, P5902
[7]  
Dean M, 2001, J LIPID RES, V42, P1007
[8]   Probing tumor phenotypes using stable and regulated synthetic microRNA precursors [J].
Dickins, RA ;
Hemann, MT ;
Zilfou, JT ;
Simpson, DR ;
Ibarra, I ;
Hannon, GJ ;
Lowe, SW .
NATURE GENETICS, 2005, 37 (11) :1289-1295
[9]   Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells [J].
Ferretti, Elisabetta ;
De Smaele, Enrico ;
Miele, Evelina ;
Laneve, Pietro ;
Po, Agnese ;
Pelloni, Marianna ;
Paganelli, Arianna ;
Di Marcotullio, Lucia ;
Caffarelli, Elisa ;
Screpanti, Isabella ;
Bozzoni, Irene ;
Gulino, Alberto .
EMBO JOURNAL, 2008, 27 (19) :2616-2627
[10]   Multidrug resistance in cancer: Role of ATP-dependent transporters [J].
Gottesman, MM ;
Fojo, T ;
Bates, SE .
NATURE REVIEWS CANCER, 2002, 2 (01) :48-58