Cancer stem-like cells have cisplatin resistance and miR-93 regulate p21 expression in breast cancer

Abstract

Aim: This study aims to examine the role of microRNAs (miRNAs) in regulating the expression of p21, a cyclin-dependent kinase inhibitor, and in inducing resistance to cisplatin, an anticancer drug. Methods: Human breast cancer cell line MDA-MB231 cells were separated into two subpopulations, cancer stem-like cells (CSCs) and cancer cells, based on the expression of cell surface antigens CD44 and CD24. Results: p21 protein expression was higher in CSCs than in cancer cells. Exposure of MDA-MB-231 cells to cisplatin increased p21 protein expression. However, p21 expression was significantly lower in cisplatin-treated CSCs than in cisplatin-treated cancer cells, suggesting that p21-dependent cell cycle suppression was lower in CSCs than in cancer cells. Moreover, caspase-3 activity was significantly lower in cisplatin-treated CSCs than in cisplatin-treated cancer cells, indicating that CSCs were more resistant to cisplatin-induced apoptosis than cancer cells. Treatment with miR-93 inhibitors increased p21 expression in CSCs, suggesting that miR-93 suppressed p21 expression. Conclusion: The results of the present study indicate that CSCs contribute to cisplatin resistance of MDA-MB231 cells and suggest that miR-93 inhibits the expression of p21, a factor involved in drug resistance.