title: Regulation of miR-19 to breast cancer chemoresistance through targeting PTEN.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Radiology and Imaging Sciences, Emory University, Atlanta, Georgia 30322, USA. zliang@emory.edu
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liang
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Li
authors.forename: Ke
authors.initials: K
authors.lastname: Huang
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wagar
authors.forename: Hyunsuk
authors.initials: H
authors.lastname: Shim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001940:Breast / Q000187:drug effects / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C549214:MIRN19A microRNA, human; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human