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. What's new? As for normal cells, autophagy is critical for tumor cells to survive stressful conditions, and thus has been implicated in tumor resistance to chemotherapy and radiotherapy. The present study showed that miR-200c could sensitize breast cancer cells to radiation via a mechanism associated with inhibition of irradiation-induced autophagy. The authors also identified ubiquilin 1 (UBQLN1) as a link between miR-200c, autophagy, and radioresistance of breast cancer cells. These results provide new insights into the molecular functions of miR-200c in the radiosensitivity of breast cancer cells and offer a rationale for enhancing radiosensitivity via miR-200c for the treatment of breast cancer.