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

Zhongxing Liang, Hui Wu, James Xia, Yuhua Li, Yawei Zhang, Ke Huang, Nicholas Wagar, Younghyoun Yoon, Heidi T. Cho, Stefania Scala, Hyunsuk Shim

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)817-824
Number of pages8
JournalBiochemical Pharmacology
Volume79
Issue number6
DOIs
Publication statusPublished - Mar 15 2010

Keywords

  • Breast cancer
  • microRNA
  • MRP-1
  • Multidrug resistance

ASJC Scopus subject areas

  • Pharmacology
  • Biochemistry

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