MicroRNA-34a Modulates Chemosensitivity of Breast Cancer Cells to Adriamycin by Targeting Notch1

Background and Aims. MicroRNA-34a (miR-34a) as a tumor suppressor has been reported in many other studies. However, its role in modulating the sensitivity of breast cancer cells to adriamycin (ADR) remains unclear. The aim of this study is to evaluate the role of miR-34a in the sensitivity of breast cancer cells to ADR. Methods. The role of miR-34a in breast cancer cells was detected using MTT assay, flow cytometry assay, real-time PCR and Western blot, etc. The association of miR-34a and Notch1 was analyzed by dual-luciferase reporter assay and Notch1-siRNA technology. Real-time PCR assay was performed to test the expression of miR-34a and Notch] in 38 selective breast cancer tissue samples. Results. Ectopic overexpression of miR-34a could sensitize MCF-7 breast cancer cells to ADR. MiR-34a mimic could inhibit the luciferase activity of the construct containing wild-type 3 ' UTR of Notch1 in MCF-7/ADR cells. Notch1-siRNA could partially reverse the effect of miR-34a inhibitor in inducing chemoresistance of MCF-7 cells to ADR. Further, there was an inverse association between Notch1 and miR-34a expression in breast cancer. Conclusion. Dysregulation of miR-34a plays critical roles in the acquired ADR resistance of breast cancer, at least in part via targeting Notch1. (C) 2012 MISS. Published by Elsevier Inc.