Hsa-miR-599 inhibits breast cancer progression via BRD4/Jagged1/Notch1 axis

J Cell Physiol. 2022 Jan;237(1):523-531. doi: 10.1002/jcp.30548. Epub 2021 Aug 20.

Abstract

Hsa-miR-599 was identified as a tumor suppressor against cancer. This study aimed to explore possible mechanisms of antitumor effect of hsa-miR-599 against breast cancer. Tissue specimens were collected from 106 breast cancer cases, and breast cancer cell line MCF-7 was cultured for in vitro experiments. The expression pattern of hsa-miR-599 was measured via quantitative real-time polymerase chain reaction. Lipofectamine® 2000 reagent was used for cell transfection. Cell viability, motility and apoptosis were detected using MTT assay, transwell assay, and flow cytometer, respectively. Protein analysis was performed via western blot. Hsa-miR-599 expression was decreased in breast cancer tissues and cells. Moreover, its expression was negatively correlated with TNM stage (p = 0.004) and lymph node metastasis (p = 0.001). Enhanced hsa-miR-599 expression in breast cancer cells could induce the inhibition against cell proliferation, migration and invasion, and strengthen cell apoptosis. BRD4 might be a target of hsa-miR-599. Hsa-miR-599 combined with BRD4 inhibited breast cancer progression through targeting Jagged1/Notch1 pathway. Hsa-miR-599 expression is downregulated in breast cancer. Hsa-miR-599 may inactivate BRD4/Jagged1/Notch1 axis, thus suppressing malignant progression of breast cancer.

Keywords: BRD4; Hsa-miR-599; Jagged1/Notch1; breast cancer; microRNAs.

MeSH terms

  • Breast Neoplasms* / pathology
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • BRD4 protein, human
  • Cell Cycle Proteins
  • MIRN599 microRNA, human
  • MicroRNAs
  • NOTCH1 protein, human
  • Nuclear Proteins
  • Receptor, Notch1
  • Transcription Factors