MiR-489 regulates chemoresistance in breast cancer via epithelial mesenchymal transition pathway

• miR-489 was significantly suppressed in MCF-7/ADM cells compared with parental control MCF-7/WT cells.
• Forced-expression of miR-489 reversed the chemoresistance.
• Smad3 was the target of miR-489 and was highly expressed in MCF-7/ADM cells.
• Forced expression of miR-489 inhibited Smad3 expression and EMT properties.
• The gene/miRNA expression changes were confirmed in human breast tumor xenografts and in clinical samples.

To investigate the role of microRNAs in the development of chemoresistance and related epithelial–mesenchymal transition (EMT), we examined the effect of miR-489 in adriamycin (ADM)-resistant human breast cancer cells (MCF-7/ADM). MiR-489 was significantly suppressed in MCF-7/ADM cells compared with chemosensitive parental control MCF-7/WT cells. Forced-expression of miR-489 reversed chemoresistance. Furthermore, Smad3 was identified as the target of miR-489 and is highly expressed in MCF-7/ADM cells. Forced expression of miR-489 both inhibited Smad3 expression and Smad3 related EMT properties. Finally, the interactions between Smad3, miR-489 and EMT were confirmed in chemoresistant tumor xenografts and clinical samples, indicating their potential implication for treatment of chemoresistance.