miR-219a-5p inhibits breast cancer cell migration and epithelial-mesenchymal transition by targeting myocardin-related transcription factor A

Acta Biochim Biophys Sin (Shanghai). 2017 Dec 1;49(12):1112-1121. doi: 10.1093/abbs/gmx114.

Abstract

Although many miRNAs are reported to be involved in tumor formation and progression, the effect of miR-219a-5p on breast cancer metastasis is not well-known. The aim of this study is to investigate the effect of miR-219a-5p on the migratory ability and epithelial-mesenchymal transition (EMT) of breast cancer cells. First, miR-219a-5p was found to be highly expressed in low-invasive breast cancer MCF-7 cells, but lowly expressed in high-invasive breast cancer MDA-MB-231 cells. Wound scratch assay and transwell assay showed that miR-219a-5p inhibited the migratory ability of MDA-MB-231 cells. miR-219a-5p also suppressed the cellular EMT, confirmed by suppressing the expression of mesenchymal markers vimentin and N-cadherin and increasing the expression of epithelial marker E-cadherin. Using the epithelial-mesenchymal-epithelial model in MCF-7 cells, we confirmed that the level of miR-219a-5p was highly expressed in epithelial-type cells and lowly expressed in mesenchymal-type cells. Importantly, we identified myocardin-related transcription factor A (MRTF-A) as a novel potential target gene of miR-219a-5p. Overexpression of miR-219a-5p in MDA-MB-231 cells could inhibit the expression of MRTF-A as revealed by real-time PCR and western blot analysis. miR-219a-5p inhibited the transcription of MRTF-A by targeting the 3'UTR of MRTF-A, which was confirmed by wild-type or mutant MRTF-A 3'UTR luciferase reporter system. Furthermore, knockdown of MRTF-A using siRNA for MRTF-A could depress breast cell migration. In conclusion, our present study revealed the tumor suppressive role of miR-219a-5p in regulating breast cancer migration by targeting MRTF-A, suggesting that miR-219a-5p might be a therapeutic target in breast cancer through regulating EMT.

Keywords: breast cancer; cell migration; epithelial-mesenchymal transition; miR-219a-5p; myocardin-related transcription factor A.

MeSH terms

  • Breast Neoplasms / pathology*
  • Cell Movement
  • Epithelial-Mesenchymal Transition*
  • Female
  • Genes, Tumor Suppressor / physiology*
  • Hep G2 Cells
  • Humans
  • MCF-7 Cells
  • MicroRNAs / physiology*
  • Neoplasm Metastasis
  • Trans-Activators / genetics*

Substances

  • MIRN219 microRNA, human
  • MRTFA protein, human
  • MicroRNAs
  • Trans-Activators