Involvement of miR-326 in chemotherapy resistance of breast cancer through modulating expression of multidrug resistance-associated protein 1 |
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Authors: | Zhongxing Liang Hui Wu Yuhua Li Ke Huang Younghyoun Yoon Stefania Scala |
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Institution: | a Department of Radiology, Emory University, Atlanta, GA 30322, USA b GenoSensor Corporation, 4665 S. Ash Ave., Suite G-18, Tempe, AZ 85282, USA c Yerkes Microarray Core, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA d Cancer Hospital/Institute, Fudan University, Shanghai 200032, China e Department of Clinical Immunology, National Cancer Institute, G. Pascale Foundation, via Mariano Semmola, 80131 Naples, Italy f Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA |
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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. |
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