Suppressive role of miR-592 in breast cancer by repressing TGF-β2

Oncol Rep. 2017 Dec;38(6):3447-3454. doi: 10.3892/or.2017.6029. Epub 2017 Oct 12.

Abstract

The function of miR-592 has been investigated in many types of cancer, however its roles in breast cancer remain unclear. We therefore investigated the biological function and underlying mechanism of miR-592 in breast cancer. In the present study, a marked downregulation of miR-592 was observed in breast cancer tissues and cell lines compared to the matched adjacent non-tumor tissues and normal breast cell line. Statistical analysis revealed that decreased miR-592 was negatively associated with advanced clinical stage, distant metastasis and lymph node metastases. Function analysis demonstrated that overexpression of miR-592 significantly inhibited cell proliferation, clone formation, migration and invasion in breast cancer cells in vitro, as well as suppressed tumor growth in vivo. Furthermore, transforming growth factor β-2 (TGFβ-2), a known oncogene, was identified as a direct target of miR-592, and its mRNA expression level was inversely correlated with the expression level of miR-592 in human breast cancer specimens. Restoration of TGFβ-2 expression rescued the inhibitory effect in breast cancer cells caused by miR-592. Collectively, these data suggest that miR-592 may exert it suppressive role in breast cancer, at least in part, by targeting TGFβ-2, and that miR-592 may be a novel target for breast cancer treatment.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis
  • Mice
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Transforming Growth Factor beta1 / genetics*
  • Xenograft Model Antitumor Assays

Substances

  • MIRN592 microRNA, human
  • MicroRNAs
  • TGFB1 protein, human
  • Transforming Growth Factor beta1