Regulation of miR-19 to breast cancer chemoresistance through targeting PTEN.

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.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

Liang Z,Li Y,Huang K,Wagar N,Shim H

doi

10.1007/s11095-011-0570-y

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

3091-100

issue

12

eissn

0724-8741

issn

1573-904X

journal_volume

28

pub_type

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