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

Liu,Yanting; Chu,Zhaowei; Li,Qingyan; Peng,Bin; Xu,Suyun; Lian,Christine G.; Geng,Songmei

doi:10.3892/or.2016.5244

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

Authors:
- Yanting Liu
- Zhaowei Chu
- Qingyan Li
- Bin Peng
- Suyun Xu
- Christine G. Lian
- Songmei Geng
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Affiliations: Department of Dermatology, Northwest Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
Published online on: November 15, 2016 https://doi.org/10.3892/or.2016.5244
Pages: 139-146

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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.

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