miR-497 inhibits epithelial mesenchymal transition in breast carcinoma by targeting Slug

Tumour Biol. 2016 Jun;37(6):7939-50. doi: 10.1007/s13277-015-4665-7. Epub 2015 Dec 23.

Abstract

Epithelial to mesenchymal transition (EMT) is a critical step in the growth and dissemination of malignant diseases, including breast cancer. It is known that microRNAs (miRNAs) play important roles in the regulation of tumor properties in cancers. However, whether miR-497 contributes to EMT in breast cancer cells remains unknown. Our study demonstrated that the expression of miR-497 was significantly decreased in human breast cancer cell lines and breast cancer specimens. In breast cancer cells, EMT was inhibited and promoted by the over-expression as well as depletion of miR-497, respectively. Dual-Luciferase ReporterAassay confirmed that Slug was a direct target of miR-497. The upregulation of miR-497 in breast cancer cells suppressed cell proliferation and induced apoptosis both in vitro and in vivo. Correlation analysis indicated that miR-497 was highly negatively correlated with Slug expression in breast cancer specimens. The knockdown of Slug expression in breast cancer cells significantly suppressed cell proliferation and promoted apoptosis. Our results suggested that the expression of miR-497 is significantly correlated with EMT in breast cancer cells by regulating Slug at the transcriptional as well as translational levels. Therefore, targeting miR-497 may provide a novel strategy for the treatment of breast cancer.

Keywords: Apoptosis; Breast cancer; EMT; Slug; miR-497.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Blotting, Western
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Mice, Inbred BALB C
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Snail Family Transcription Factors / genetics*
  • Snail Family Transcription Factors / metabolism
  • Transfection
  • Wound Healing

Substances

  • MIRN497 microRNA, human
  • MicroRNAs
  • SNAI1 protein, human
  • Snail Family Transcription Factors