Regulation of miR-19 to Breast Cancer Chemoresistance Through Targeting PTEN
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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.
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.
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.
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.
KEY WORDSbreast cancer microRNA multidrug resistance PTEN
breast cancer resistance protein
locked nucleic acid
multidrug resistance 1
multidrug resistance-associated protein 1
phosphatase and tensin homolog
reverse transcription polymerase chain reaction.