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

Technol Cancer Res Treat. 2020 Jan-Dec:19:1533033820927011. doi: 10.1177/1533033820927011.

Abstract

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.

Keywords: TNBC; YAP1; YES1; miR-133.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics*
  • Middle Aged
  • Phosphorylation
  • Prognosis
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-yes / genetics
  • Proto-Oncogene Proteins c-yes / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology*
  • Triple Negative Breast Neoplasms / surgery
  • Tumor Cells, Cultured
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • MAS1 protein, human
  • MIRN133 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Mas
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Proto-Oncogene Proteins c-yes
  • YES1 protein, human