MiR-129-5p is downregulated in breast cancer cells partly due to promoter H3K27m3 modification and regulates epithelial-mesenchymal transition and multi-drug resistance

Eur Rev Med Pharmacol Sci. 2016 Oct;20(20):4257-4265.


Objective: In this study, we firstly studied whether H3K27me3 modification is a mechanism of miR-129-5p downregulation in breast cancer and further investigated the functional role of miR-129-5p in epithelial-to-mesenchymal transition (EMT) and in multi-drug resistance (MDR) of the cancer cells.

Materials and methods: Immunoprecipitation (IP) and Chromatin Immunoprecipitation (ChIP) assay were performed to detect the association among SOX4, EZH2 and H3K27me3 and their enrichment in the promoter region of miR-129-2. Western blot and immunofluorescent staining were performed to detect the expression of epithelial and mesenchymal markers. MTT assay was applied to test drug sensitivity.

Results: Enforced EZH2 and SOX4 expression resulted in suppressed miR-129-5p level in MCF-7 cells. There was an interaction among SOX4, EZH2 and H3K27me3 modification and they were significantly enriched in the region upstream of transcription start of miR-129-2. MCF-7 cells transfected with miR-129-5p mimics had significantly suppressed SOX4 expression. MCF-7 cells with miR-129-5p overexpression had significantly restored E-cadherin expression and suppressed N-cadherin and Vimentin expression. The drug sensitivity assay showed that miR-129-5p substantially reduced IC50 of ADM, VCR and PTX in MCF-7/ADM cells CONCLUSIONS: There is a reciprocal regulation between miR-129-5p and SOX4 via the SOX4/EZH2 complex mediated H3K27me3 modification in breast cancer cells. MiR-129-5p is an important miRNA modulating EMT and MDR in breast cancer cells.

MeSH terms

  • Breast Neoplasms / genetics*
  • Down-Regulation
  • Drug Resistance, Multiple*
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • Promoter Regions, Genetic
  • SOXC Transcription Factors


  • MicroRNAs
  • Mirn129 microRNA, human
  • SOX4 protein, human
  • SOXC Transcription Factors