Depletion of B cell CLL/Lymphoma 11B Gene Expression Represses Glioma Cell Growth

Autor: Chin Hsien Wu, Kitman Chai, Chia Hsin Ho, Shun Fen Tzeng, Chih Kai Liao, Kuan Min Fang, Chung Shi Yang
Rok vydání: 2015
Předmět:
Cyclin-Dependent Kinase Inhibitor p21
0301 basic medicine
Carcinogenesis
BCL11B
T cell
Neuroscience (miscellaneous)
Down-Regulation
Biology
Flow cytometry
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Cell Movement
Cell Line
Tumor
Glioma
medicine
Animals
Humans
Propidium iodide
neoplasms
Cellular Senescence
Cell Proliferation
Polycomb Repressive Complex 1
Gene knockdown
medicine.diagnostic_test
Brain Neoplasms
SOXB1 Transcription Factors
Tumor Suppressor Proteins
BCL11B Gene
Cell Cycle Checkpoints
Cell cycle
medicine.disease
Rats
Up-Regulation
nervous system diseases
Gene Expression Regulation
Neoplastic
Repressor Proteins
030104 developmental biology
medicine.anatomical_structure
Neurology
chemistry
Gene Knockdown Techniques
Cancer research
Tumor Suppressor Protein p53
Zdroj: Molecular Neurobiology. 53:3528-3539
ISSN: 1559-1182
0893-7648
DOI: 10.1007/s12035-015-9231-1
Popis: B cell CLL/lymphoma 11B (Bcl11b), a C2H2 zinc finger transcription factor, not only serves as a critical regulator in development but also plays the controversial role in T cell acute lymphoblastic leukemia (T-ALL). We previously found that the enriched expression of Bcl11b was detected in high tumorigenic C6 glioma cells. However, the role of Bcl11b in glioma malignancy and its mechanisms remains to be uncovered. In this study, using the lentivirus-mediated knockdown (KD) approach, we found that Bcl11b KD in tumorigenic C6 cells reduced the cell proliferation, colony formation, and migratory ability. The results were further verified using two human malignant glioma cell lines, U87 and U251 cells. A cyclin-dependent kinase inhibitor p21, a known Bcl11b target, was significantly upregulated in tumorigenic C6, U87, and U251 cells after Bcl11b KD. Cellular senescence was observed by examination of the β-galactosidase activity in U87 and U251 cells with Bcl11b KD. Reduced expression of stemness gene Sox-2 and its downstream effector Bmi-1 was also observed in U87 and U251 cells with Bcl11b KD. These results suggest that the ablation of Bcl11b gene expression induced glioma cell senescence. Propidium iodide (PI) staining combined with flow cytometry analysis also showed that Bcl11b KD led to the cell cycle arrest of U87 and U251 cells at the G0/G1 or at the S phase, indicating that Bcl11b is required for glioma cell cycle progression. Together, this is the first study to show that the inhibition of Bcl11b suppresses glioma cell growth by regulating the expression of the cell cycle regulator p21 and stemness-associated genes (Sox-2/Bmi-1).
Databáze: OpenAIRE
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