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.
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.
Authors: Lixin Hong; Maoyi Lai; Michelle Chen; Changchuan Xie; Rong Liao; Young Jun Kang; Changchun Xiao; Wen-Yuan Hu; Jiahuai Han; Peiqing Sun Journal: Cancer Res Date: 2010-09-17 Impact factor: 12.701
Authors: D A Brown; S H Kang; S M Gryaznov; L DeDionisio; O Heidenreich; S Sullivan; X Xu; M I Nerenberg Journal: J Biol Chem Date: 1994-10-28 Impact factor: 5.157
Authors: Gergely Szakács; Jill K Paterson; Joseph A Ludwig; Catherine Booth-Genthe; Michael M Gottesman Journal: Nat Rev Drug Discov Date: 2006-03 Impact factor: 84.694
Authors: Olga Kovalchuk; Jody Filkowski; James Meservy; Yaroslav Ilnytskyy; Volodymyr P Tryndyak; Vasyl' F Chekhun; Igor P Pogribny Journal: Mol Cancer Ther Date: 2008-07 Impact factor: 6.261
Authors: Genesio M Karere; Jeremy P Glenn; Shifra Birnbaum; Sassan Hafizi; David L Rainwater; Michael C Mahaney; John L VandeBerg; Laura A Cox Journal: J Lipid Res Date: 2013-04-17 Impact factor: 5.922