Triple-negative breast cancer shows worse outcome compared with other subtypes of breast cancer. The discovery of dysregulated microRNAs and their roles in the progression of triple-negative breast cancer provide novel strategies for the treatment of patients with triple-negative breast cancer. In this study, we identified the significant reduction of miR-133 in triple-negative breast cancer tissues and cell lines. Ectopic overexpression of miR-133 suppressed the proliferation, colony formation, and upregulated the apoptosis of triple-negative breast cancer cells. Mechanism study revealed that the YES Proto-Oncogene 1 was a target of miR-133. miR-133 bound the 3′-untranslated region of YES Proto-Oncogene 1 and decreased the level of YES Proto-Oncogene 1 in triple-negative breast cancer cells. Consistent with miR-133 downregulation, YES1 was significantly increased in triple-negative breast cancer, which was inversely correlated with the level of miR-133. Restoration of YES Proto-Oncogene 1 attenuated the inhibitory effects of miR-133 on the proliferation and colony formation of triple-negative breast cancer cells. Consistent with the decreased expression of YES Proto-Oncogene 1, overexpression of miR-133 suppressed the phosphorylation of YAP1 in triple-negative breast cancer cells. Our results provided novel evidence for the role of miR-133/YES1 axis in the development of triple-negative breast cancer, which indicated miR-133 might be a potential therapeutic strategy for triple-negative breast cancer.

与其他亚型乳腺癌相比，三阴性乳腺癌的预后较差。失调的microRNA的发现及其在三阴性乳腺癌进展中的作用为三阴性乳腺癌患者的治疗提供了新的策略。在这项研究中，我们确定了三阴性乳腺癌组织和细胞系中miR-133的显着降低。miR-133的异位过表达抑制了三阴性乳腺癌细胞的增殖，集落形成并上调了细胞凋亡。机制研究表明，YES原癌基因1是miR-133的靶标。miR-133结合了YES原癌基因1的3'非翻译区，并降低了三阴性乳腺癌细胞中YES原癌基因1的水平。与miR-133下调一致，YES1在三阴性乳腺癌中显着增加，这与miR-133的水平呈负相关。YES原癌基因1的恢复减弱了miR-133对三阴性乳腺癌细胞增殖和集落形成的抑制作用。与YES原癌基因1的表达减少相一致，miR-133的过表达抑制了三阴性乳腺癌细胞中YAP1的磷酸化。我们的结果为miR-133 / YES1轴在三阴性乳腺癌发展中的作用提供了新的证据，这表明miR-133可能是三阴性乳腺癌的潜在治疗策略。YES原癌基因1的恢复减弱了miR-133对三阴性乳腺癌细胞增殖和集落形成的抑制作用。与YES原癌基因1的表达减少相一致，miR-133的过表达抑制了三阴性乳腺癌细胞中YAP1的磷酸化。我们的结果为miR-133 / YES1轴在三阴性乳腺癌发展中的作用提供了新的证据，这表明miR-133可能是三阴性乳腺癌的潜在治疗策略。YES原癌基因1的恢复减弱了miR-133对三阴性乳腺癌细胞增殖和集落形成的抑制作用。与YES原癌基因1的表达减少相一致，miR-133的过表达抑制了三阴性乳腺癌细胞中YAP1的磷酸化。我们的结果为miR-133 / YES1轴在三阴性乳腺癌发展中的作用提供了新的证据，这表明miR-133可能是三阴性乳腺癌的潜在治疗策略。