title: Bmi-1 promotes glioma angiogenesis by activating NF-κB signaling.
abstract: Angiogenesis in glioma is associated with the poor prognosis of the disease and closely correlates with the highly invasive phenotype of glioma cells, which represents the most challenging impediment against the currently glioma treatments. Bmi-1, an onco-protein, has been implicated in the progression of various human cancers, including gliomas, whereas its role in glioma angiogenesis remains unclear. Our current study examined the effects of Bmi-1 on glioma angiogenesis in vitro as well as in vivo. We found that overexpression of Bmi-1 enhanced, whereas knockdown of Bmi-1 diminished, the capability of glioma cells to induce tubule formation and migration of endothelial cells and neovascularization in chicken chorioallantoic membrane. In vivo, Bmi-1 overexpression and knockdown, respectively, promoted and inhibited angiogenesis in orthotopically transplanted human gliomas. Furthermore, NF-κB activity and VEGF-C expression was induced by Bmi-1 overexpression, whereas Bmi-1 knockdown attenuated NF-κB signaling and decreased VEGF-C expression. Additionally suppression of NF-κB activity using a specific chemical inhibitor abrogated the NF-κB activation and the pro-angiogenic activities of glioma cells. Together, our data suggest that Bmi-1 plays an important role in glioma angiogenesis and therefore could represent a potential target for anti-angiogenic therapy against the disease.
authors: Department of Pathophysiology, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors: Lili
authors: L
authors: Jiang
authors: Libing
authors: L
authors: Song
authors: Jueheng
authors: J
authors: Wu
authors: Yi
authors: Y
authors: Yang
authors: Xun
authors: X
authors: Zhu
authors: Bo
authors: B
authors: Hu
authors: Shi-Yuan
authors: SY
authors: Cheng
authors: Mengfeng
authors: M
authors: Li
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002642:Chick Embryo; D004789:Enzyme Activation; D015870:Gene Expression; D020868:Gene Silencing; D005910:Glioma / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics*; D063150:Polycomb Repressive Complex 1 / Q000235:genetics*; D034622:RNA Interference; D015398:Signal Transduction; D014183:Transplantation, Heterologous; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism
chemical_list: C069077:BMI1 protein, human; D016328:NF-kappa B; D042582:Vascular Endothelial Growth Factor C; D063150:Polycomb Repressive Complex 1
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