Downregulation of Bmi-1 suppresses epithelial‑mesenchymal transition in melanoma

Oncol Rep. 2017 Jan;37(1):139-146. doi: 10.3892/or.2016.5244. Epub 2016 Nov 15.

Abstract

Epithelial-mesenchymal transition (EMT) contributes to the invasion and metastasis of numerous malignant cancers, including melanoma. A significant higher expression of B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1) has been reported in cell lines from metastatic melanoma compared to cell lines from primary melanoma. There are studies that show that knockdown of Bmi-1 could induce E-cadherin expression in melanoma cells. However, the role of Bmi-1 in mediating EMT-like changes in melanoma has not yet been fully studied. In the present study, knockdown of Bmi-1 by shRNA transduction decreased the invasion properties of the cultured human melanoma cells A375 by a Matrigel invasion assay, along with alterations in EMT-related markers E-cadherin, α-catenin, vimentin and N-cadherin. The aforementioned altered expression of EMT markers was verified in BALB/c-nude mouse xenografts. Furthermore, to explore the underlying regulatory mechanism of EMT, we detected the significant downregulation of p-Akt/p‑NF-κB/MMP-2 and the upregulation of PTEN in Bmi-1-silenced A375 cells. The present study demonstrated that knockdown of Bmi-1 significantly inhibited the aggressive behavior of melanoma by reversing EMT-like changes via the PTEN/p-Akt/p‑NF-κB/MMP-2 pathway.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Melanoma / genetics*
  • Melanoma / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Metastasis
  • Polycomb Repressive Complex 1 / antagonists & inhibitors
  • Polycomb Repressive Complex 1 / genetics*
  • Signal Transduction / genetics
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology*
  • Xenograft Model Antitumor Assays

Substances

  • BMI1 protein, human
  • Polycomb Repressive Complex 1