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

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

来源：Oncology Reports, 2017, 37(1): 139-146.

DOI：10.3892/or.2016.5244

• Bmi-1
• epithelial-mesenchymal transition
• melanoma
• PTEN
• NF-kappa B

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, alpha-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-kappa B/MMP-2 and the upregulation of PTEN in Bmi-l-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-kappa B/MMP-2 pathway.

• 出版日期2017-1
• 单位西安交通大学