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Bmi-1 promotes the aggressiveness of glioma via activating the NF-kappaB/MMP-9 signaling pathway.
- Source :
-
BMC Cancer . 2012, Vol. 12 Issue 1, p406-417. 12p. 7 Diagrams. - Publication Year :
- 2012
-
Abstract
- Background: The prognosis of human glioma is poor, and the highly invasive nature of the disease represents a major impediment to current therapeutic modalities. The oncoprotein B-cell-specific Moloney murine leukemia virus integration site 1 protein (Bmi-1) has been linked to the development and progression of glioma; however, the biological role of Bmi-1 in the invasion of glioma remains unclear. Methods: A172 and LN229 glioma cells were engineered to overexpress Bmi-1 via stable transfection or to be silenced for Bmi-1 expression using RNA interfering method. Migration and invasiveness of the engineered cells were assessed using wound healing assay, Transwell migration assay, Transwell matrix penetration assay and 3-D spheroid invasion assay. MMP-9 expression and activity were measured using real-time PCR, ELISA and the gelatin zymography methods. Expression of NF-kappa B target genes was quantified using real-time PCR. NF-kappaBtranscriptional activity was assessed using an NF-kappaB luciferase reporter system. Expression of Bmi-1 and MMP-9 in clinical specimens was analyzed using immunohistochemical assay.Results: Ectopic overexpression of Bmi-1 dramatically increased, whereas knockdown of endogenous Bmi-1reduced, the invasiveness and migration of glioma cells. NF-kappaB transcriptional activity and MMP-9 expression and activity were significantly increased in Bmi-1-overexpressing but reduced in Bmi-1-silenced cells. The reporter luciferase activity driven by MMP-9 promoter in Bmi-1-overexpressing cells was dependent on the presence of a functional NF-kappaB binding site, and blockade of NF-kappa B signaling inhibited the up regulation of MMP-9 in Bmi-1 overexpressing cells. Furthermore, expression of Bmi-1 correlated with NF-kappaB nuclear translocation as well as MMP-9 expression in clinical glioma samples.Conclusions: Bmi-1 may play an important role in the development of aggressive phenotype of glioma via activating the NF-kappaB/MMP-9 pathway and therefore might represent a novel therapeutic target for glioma. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14712407
- Volume :
- 12
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- BMC Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 84523346
- Full Text :
- https://doi.org/10.1186/1471-2407-12-406