Silencing of Bmi-1 Gene Enhances Chemotherapy Sensitivity in Human Glioblastoma Cells

Hong, Yang; Shang, Chao; Xue, Yixue; Liu, Yunhui

doi:10.12659/msm.893754

Cited by 15 publications

(8 citation statements)

References 21 publications

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“…High levels of therapy resistance, strong cellular invasiveness, and rapid cell growth demand aggressive multimodal therapies involving resection followed by radio-chemotherapy [ 2 , 3 ]. Although the treatment strategies have been improved remarkably, including surgical equipment or adjuvant therapy, the overall survival rate of GBM is still very poor and new therapies are urgently needed [ 4 – 6 ]. The finding of new biomarkers can help discover new targeted drugs and therapies.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Significance of Zinc Finger E-Box-Binding Homeobox Family in Glioblastoma

et al. 2018

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BackgroundEpithelial-mesenchymal transition (EMT) is an essential progress for tumor cell invasion to both epithelial and non-epithelial cancers, and zinc finger E-box-binding homeobox 1/2 (ZEB1/2) is a well-known promoter of EMT. In glioma cell lines, both ZEB1 and ZEB2 have been demonstrated to facilitate cancer cell proliferation and invasion with experiments in vitro. However, the clinical significance of ZEB1 and ZEB2 in glioblastoma (GBM) is still controversial.Material/MethodsWe detected the expression of ZEB1 and ZEB2 in 91 cases of GBM with immunohistochemistry and investigated the correlation between clinicopathological factors and ZEB family expression with Fisher test. By univariate analysis with Kaplan-Meier test, we explored the prognostic significance of ZEB1/2 expression and the clinicopathological factors in GBM. By multivariate analysis with the Cox regression model, we identified the independent prognostic factors in GBM.ResultsThe percentages of ZEB1 high expression and ZEB2 high expression were 31.9% (29/91) and 41.9% (36/91), respectively. High expression of ZEB2 was significantly associated with lower survival rate of GBM patients (P=0.001). ZEB2, lower KPS score (P=0.004), gross total resection (P<0.001) and higher Ki67 percentage (P=0.001) were notably correlated to worse prognosis of GBM. With multivariate analysis, high expression of ZEB2 was demonstrated to be an independent prognostic factor indicating unfavorable prognosis of GBM (P=0.001, HR=3.86, and 95%CI=1.61–9.23).ConclusionsHigh expression of ZEB2 is an independent prognostic factor predicting unfavorable prognosis of GBM, indicating that ZEB2 or its downstream proteins may be potential drug targets of GBM therapy.

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Section: Introductionmentioning

confidence: 99%

Prognostic Significance of Zinc Finger E-Box-Binding Homeobox Family in Glioblastoma

et al. 2018

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“…It was demonstrated that the silencing of BMI-1 may significantly inhibit A-431 cell proliferation through the promotion of apoptosis. Numerous studies have revealed that BMI-1 has a role in tumor development, invasion and metastasis ( 11 – 14 , 18 ). Destruction of the extracellular matrix and migration into the vascular system are key steps required for tumor metastasis ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have demonstrated that BMI-1 expression, which is upregulated in multiple types of cancer, is positively correlated with clinical grade/stage and poor prognosis in cervical ( 7 ), ovarian ( 8 ), endometrial ( 9 ) and lung ( 10 ) cancer. Silencing of BMI-1 expression by RNA interference (RNAi) has been observed to decrease the rate of tumor cell growth, resulting in cell cycle arrest and inhibition of the invasive ability of tumor cells ( 11 – 14 ). In the present study, BMI-1 expression in VSCC was examined, and the effect of small-interfering RNA (siRNA)-mediated silencing of BMI-1 in A-431 cells was investigated.…”

Section: Introductionmentioning

confidence: 99%

Expression of B cell-specific Moloney murine leukemia virus integration site 1 in vulvar squamous cell carcinoma and its effect on the biological behavior of A-431 cells

Bai

Ouyang

et al. 2015

Oncology Letters

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The aim of the present study was to investigate the expression of B cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) in vulvar squamous cell carcinoma (VSCC) and vulvar intraepithelial neoplasia (VIN). Furthermore, the present study investigated the effects of BMI-1 expression on the biological behavior of A-431 human epidermoid carcinoma cells. BMI-1 expression in human VSCC and VIN tissues was detected using immunohistochemistry. Subsequently, BMI-1 expression was silenced in A-431 cells using small interfering RNA (siRNA), and BMI-1 expression was detected using reverse transcription-quantitative polymerase chain reaction and western blotting. The effects of BMI-1 silencing on cell proliferation, apoptosis and invasive ability were determined using an MTT assay, Annexin V-fluorescein isothiocyanate/propidium iodide double-labeling experiment and Transwell assay, respectively. The expression rate of BMI-1 in normal vulvar, VIN and VSCC tissues was 0.0, 25.0 and 68.0% respectively, demonstrating an increasing trend in the severity of the disease. BMI-1 overexpression was found not to correlate with age, pathological stage, lymph node metastasis or degree of differentiation (P>0.05). BMI-1 siRNA transfection effectively inhibited BMI-1 messenger RNA and protein expression in A-431 cells. The mean rate of apoptosis promotion and proliferation inhibition in the most effectively silenced group were 20.19 and 46.82%, respectively, which was significantly higher than that of the cells in the blank and control siRNA groups (P<0.05). The number of invading cells was decreased in the most effectively silenced group compared with that of the blank and control siRNA groups. Abnormal expression of BMI-1 was also detected in VIN and VSCC tissues, and targeting of BMI-1 with siRNA was able to successfully silence BMI-1 expression in A-431 cells. Silencing of BMI-1 promoted apoptosis and inhibited the invasive abilities of A-431 cells in vitro.

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“…18 In addition, silencing of Bmi-1 gene led to the increased chemotherapy sensitivity of human glioblastoma (GBM) cells, and a specific inhibitor of Bmi-1, PTC-209, could significantly attenuate the glioblastoma growth in murine orthotopic xenograft model. 19,20 In consideration of PCGF1 associated with nervous system development, we were very interested in its expression and its functions in a nervous system tumor. To the best of our knowledge, there are only a few studies till date on the therapeutic potential and regulation mechanism of PCGF1 in glioblastoma (GBM) cell lines.…”

Section: Introductionmentioning

confidence: 99%

<p>Repression of PCGF1 Decreases the Proliferation of Glioblastoma Cells in Association with Inactivation of c-Myc Signaling Pathway</p>

Yan¹,

Cui²,

Dong³

et al. 2020

OTT

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Glioblastoma (GBM) is the most common primary brain tumor with a poor therapeutic outcome. Polycomb group factor 1 (PCGF1), a member of the PcG (Polycomb group) family, is highly expressed in the developing nervous system of mice. However, the function and the mechanism of PCGF1 in GBM proliferation still remain unclear. Methods: Knockdown of PCGF1 was performed in U87 GBM cell by shRNA strategy via lentivirus vector. MTT assay, colony formation assays, and flow cytometry were used to measure the properties of cell proliferation and cell cycle distribution, respectively. GeneChip analysis was performed to identify the downstream effector molecules. Rescue assay was constructed to verify the screening results. Results: We first found that knockdown of PCGF1 led to the inhibition of U87 cells proliferation and decreased colony formation ability. The data from GeneChip expression profiling and Ingenuity Pathway Analysis (IPA) indicated that many of the altered gene cells are associated with the cell proliferation control pathways. We have further confirmed the suppression of AKT/ GSK3β/c-Myc/cyclinD1 expressions by Western blotting analysis. The over-expression of c-Myc could partly restore the attenuated proliferation ability caused by knockdown of PCGF1. Conclusion: All the above evidences suggested that PCGF1 might be closely associated with tumorigenesis and progression of glioblastoma (GBM), in which process the oncoprotein c-Myc may participate. PCGF1 could thus be a potential therapeutic target for the treatment of glioblastoma (GBM).

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Silencing of Bmi-1 Gene Enhances Chemotherapy Sensitivity in Human Glioblastoma Cells

Cited by 15 publications

References 21 publications

Prognostic Significance of Zinc Finger E-Box-Binding Homeobox Family in Glioblastoma

Prognostic Significance of Zinc Finger E-Box-Binding Homeobox Family in Glioblastoma

Expression of B cell-specific Moloney murine leukemia virus integration site 1 in vulvar squamous cell carcinoma and its effect on the biological behavior of A-431 cells

<p>Repression of PCGF1 Decreases the Proliferation of Glioblastoma Cells in Association with Inactivation of c-Myc Signaling Pathway</p>

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