MiR-133 Targets YES1 and Inhibits the Growth of Triple-NegativeBreast Cancer Cells

摘要

Triple-negative breast cancer shows worse outcome compared with other subtypes ofbreast cancer. The discovery of dysregulated microRNAs and their roles in theprogression of triple-negative breast cancer provide novel strategies for thetreatment of patients with triple-negative breast cancer. In this study, weidentified the significant reduction of miR-133 in triple-negative breast cancertissues and cell lines. Ectopic overexpression of miR-133 suppressed theproliferation, colony formation, and upregulated the apoptosis oftriple-negative breast cancer cells. Mechanism study revealed that the YESProto-Oncogene 1 was a target of miR-133. miR-133 bound the 3′-untranslatedregion of YES Proto-Oncogene 1 and decreased the level of YES Proto-Oncogene 1in triple-negative breast cancer cells. Consistent with miR-133 downregulation,YES1 was significantly increased in triple-negative breast cancer, which wasinversely correlated with the level of miR-133. Restoration of YESProto-Oncogene 1 attenuated the inhibitory effects of miR-133 on theproliferation and colony formation of triple-negative breast cancer cells.Consistent with the decreased expression of YES Proto-Oncogene 1, overexpressionof miR-133 suppressed the phosphorylation of YAP1 in triple-negative breastcancer cells. Our results provided novel evidence for the role of miR-133/YES1axis in the development of triple-negative breast cancer, which indicatedmiR-133 might be a potential therapeutic strategy for triple-negative breastcancer.