title: Downregulation of Bmi-1 suppresses epithelial‑mesenchymal transition in melanoma.
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.
authors.affiliation: Department of Dermatology, Northwest Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Yanting
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Northwest Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Chu
authors.affiliation: Department of Dermatology, Northwest Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Dermatology, Northwest Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Peng
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Suyun
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Christine G
authors.initials: CG
authors.lastname: Lian
authors.affiliation: Department of Dermatology, Northwest Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Songmei
authors.initials: S
authors.lastname: Geng
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D063150:Polycomb Repressive Complex 1 / Q000037:antagonists & inhibitors / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: C069077:BMI1 protein, human; D063150:Polycomb Repressive Complex 1