caa a22 4500 445312696 CHVBK 20180317142635.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s11095-011-0570-y doi (NATIONALLICENCE)springer-10.1007/s11095-011-0570-y Regulation of miR-19 to Breast Cancer Chemoresistance Through Targeting PTEN [Elektronische Daten] [Zhongxing Liang, Yuhua Li, Ke Huang, Nicholas Wagar, Hyunsuk Shim] ABSTRACT: Purpose: To explore whether miR-19 is involved in the regulation of multidrug resistance (MDR), one of the main causes of breast cancer mortality, and modulates sensitivity of tumor cells to chemotherapeutic agents. Methods: We analyzed miRNA expression levels in three MDR cell lines in comparison with their parent cell line, MCF-7, using a miRNA microarray. We investigated whether inhibitor of miR-19 sensitized MDR cells to chemotherapeutic agents in vitro and in vivo. Results: MiR-19 was overexpressed in all three MDR cell lines compared to their parental cell line, MCF-7. Expression levels of miR-19 in MDR cells were inversely consistent with those of PTEN. Inhibitor of miR-19a restored sensitivity of MDR cells to cytotoxic agents; administration of LNA-antimiR-19a, a chemo-modified miR-19a inhibitor, sensitized MDR cells to chemotherapeutic agents in vivo. Conclusion: Our findings demonstrate, for the first time, involvement of miR-19 in multidrug resistance through modulation of PTEN and suggest that miR-19 may be a potential target for preventing and reversing MDR in tumor cells. Springer Science+Business Media, LLC, 2011 breast cancer nationallicence microRNA nationallicence multidrug resistance nationallicence PTEN nationallicence BCRP : breast cancer resistance protein nationallicence LNA : locked nucleic acid nationallicence MDR : multidrug resistance nationallicence MDR-1 : multidrug resistance 1 nationallicence miRNA : microRNA nationallicence MRP-1 : multidrug resistance-associated protein 1 nationallicence PTEN : phosphatase and tensin homolog nationallicence RT-PCR : reverse transcription polymerase chain reaction nationallicence Liang Zhongxing Department of Radiology and Imaging Sciences, Emory University, 30322, Atlanta, Georgia, USA aut Li Yuhua Yerkes Microarray Core, Yerkes National Primate Research Center Emory University, 30322, Atlanta, Georgia, USA aut Huang Ke Department of Radiology and Imaging Sciences, Emory University, 30322, Atlanta, Georgia, USA aut Wagar Nicholas Yerkes Microarray Core, Yerkes National Primate Research Center Emory University, 30322, Atlanta, Georgia, USA aut Shim Hyunsuk Department of Radiology and Imaging Sciences, Emory University, 30322, Atlanta, Georgia, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3091-3100 0724-8741 28:12<3091 2011 28 11095 https://doi.org/10.1007/s11095-011-0570-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0570-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Liang Zhongxing Department of Radiology and Imaging Sciences, Emory University, 30322, Atlanta, Georgia, USA aut NATIONALLICENCE 700 1- Li Yuhua Yerkes Microarray Core, Yerkes National Primate Research Center Emory University, 30322, Atlanta, Georgia, USA aut NATIONALLICENCE 700 1- Huang Ke Department of Radiology and Imaging Sciences, Emory University, 30322, Atlanta, Georgia, USA aut NATIONALLICENCE 700 1- Wagar Nicholas Yerkes Microarray Core, Yerkes National Primate Research Center Emory University, 30322, Atlanta, Georgia, USA aut NATIONALLICENCE 700 1- Shim Hyunsuk Department of Radiology and Imaging Sciences, Emory University, 30322, Atlanta, Georgia, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3091-3100 0724-8741 28:12<3091 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer