MiR-200c inhibits autophagy and enhances radiosensitivity in breast cancer cells by targeting UBQLN1.

Radioresistance is a major challenge during the treatment of breast cancer. A further understanding of the mechanisms of radioresistance could provide strategies to address this challenge. In our study, we compared the expression of miR-200c in four distinct breast cancer cell lines: two representative basal cancer cells (MDA-MB-231 and BT549) vs. two representative luminal cancer cells (MCF-7 and BT474). The results revealed practically lower expression of miR-200c in the two basal cancer cell lines and higher expression of miR-200c in luminal cancer cells compared to the normal breast epithelial cell line MCF-10A. Ectopic expression of miR-200c in MDA-MB-231 cells inhibited irradiation-induced autophagy and sensitized the breast cancer cells to irradiation. We also identified UBQLN1 as a direct functional target of miR-200c involved in irradiation-induced autophagy and radioresistance. In 35 human breast cancer tissue samples, we detected an inverse correlation between the expression of miR-200c vs. UBQLN1 and LC3. These results indicate that the identified miR-200c/UBQLN1-mediated autophagy pathway may help to elucidate radioresistance in human breast cancer and might represent a therapeutic strategy.