title: Depletion of B cell CLL/Lymphoma 11B Gene Expression Represses Glioma Cell Growth.
abstract: 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).
authors.affiliation: Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chih-Kai
authors.initials: CK
authors.lastname: Liao
authors.affiliation: Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Kuan-Min
authors.initials: KM
authors.lastname: Fang
authors.affiliation: Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Kitman
authors.initials: K
authors.lastname: Chai
authors.affiliation: Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chin-Hsien
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chia-Hsin
authors.initials: CH
authors.lastname: Ho
authors.affiliation: Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
authors.forename: Chung-Shi
authors.initials: CS
authors.lastname: Yang
authors.affiliation: Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan. stzeng@mail.ncku.edu.tw.
authors.forename: Shun-Fen
authors.initials: SF
authors.lastname: Tzeng
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: C479740:BCL11B protein, human; C000596384:BCL11B protein, rat; C069077:BMI1 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D063150:Polycomb Repressive Complex 1
keywords: Bcl11b; Cell senescence; Glioma; Stemness; p21