MiR-140-5p inhibits the proliferation and enhances the efficacy of doxorubicin to breast cancer stem cells by targeting Wnt1.

Abstract

MicroRNAs (miRNAs) are a group of small non-coding single-stranded RNAs molecules, the dysregulation of which plays a critical role in the initiation and biological progression of malignancies. The current study demonstrated that miR-140-5p was frequently downregulated in breast cancer stem cells (BCSCs), and miR-140-5p mimics could inhibit the proliferation of BCSCs. Moreover, Wnt1 was a direct target of miR-140-5p, as was proved by luciferase reporter assays. miR-140-5p mimics could downregulate the wnt1 mRNA and protein levels in MCF-7 and MDA-MB-231 cells. Furthermore, miR-140 mimics could enhance the sensitivity of BCSCs to doxorubicin (Dox) through the Wnt1/ABCB1 pathway both in vitro and vivo. Our findings have presented a novel miRNA-mediated regulatory network for BCSCs, which may provide a potential therapeutic target for breast cancer.