PMID- 26096706 OWN - NLM STAT- MEDLINE DCOM- 20171229 LR - 20181113 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 53 IP - 6 DP - 2016 Aug TI - Depletion of B cell CLL/Lymphoma 11B Gene Expression Represses Glioma Cell Growth. PG - 3528-3539 LID - 10.1007/s12035-015-9231-1 [doi] AB - 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 beta-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). FAU - Liao, Chih-Kai AU - Liao CK AD - Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan. FAU - Fang, Kuan-Min AU - Fang KM AD - Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan. FAU - Chai, Kitman AU - Chai K AD - Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan. FAU - Wu, Chin-Hsien AU - Wu CH AD - Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan. FAU - Ho, Chia-Hsin AU - Ho CH AD - Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan. FAU - Yang, Chung-Shi AU - Yang CS AD - Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan. FAU - Tzeng, Shun-Fen AU - Tzeng SF AD - Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan. stzeng@mail.ncku.edu.tw. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150623 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (BCL11B protein, human) RN - 0 (BCL11B protein, rat) RN - 0 (BMI1 protein, human) RN - 0 (Cyclin-Dependent Kinase Inhibitor p21) RN - 0 (Repressor Proteins) RN - 0 (SOXB1 Transcription Factors) RN - 0 (Tumor Suppressor Protein p53) RN - 0 (Tumor Suppressor Proteins) RN - EC 2.3.2.27 (Polycomb Repressive Complex 1) SB - IM MH - Animals MH - Brain Neoplasms/genetics/*pathology MH - Carcinogenesis/genetics/pathology MH - Cell Cycle Checkpoints/genetics MH - Cell Line, Tumor MH - Cell Movement/genetics MH - Cell Proliferation MH - Cellular Senescence/genetics MH - Cyclin-Dependent Kinase Inhibitor p21/genetics/metabolism MH - Down-Regulation/genetics MH - *Gene Expression Regulation, Neoplastic MH - Gene Knockdown Techniques MH - Glioma/*genetics/*pathology MH - Humans MH - Polycomb Repressive Complex 1/metabolism MH - Rats MH - Repressor Proteins/*genetics/metabolism MH - SOXB1 Transcription Factors/metabolism MH - Tumor Suppressor Protein p53/genetics/metabolism MH - Tumor Suppressor Proteins/*genetics/metabolism MH - Up-Regulation/genetics OTO - NOTNLM OT - Bcl11b OT - Cell senescence OT - Glioma OT - Stemness OT - p21 EDAT- 2015/06/23 06:00 MHDA- 2017/12/30 06:00 CRDT- 2015/06/23 06:00 PHST- 2015/03/10 00:00 [received] PHST- 2015/05/22 00:00 [accepted] PHST- 2015/06/23 06:00 [entrez] PHST- 2015/06/23 06:00 [pubmed] PHST- 2017/12/30 06:00 [medline] AID - 10.1007/s12035-015-9231-1 [pii] AID - 10.1007/s12035-015-9231-1 [doi] PST - ppublish SO - Mol Neurobiol. 2016 Aug;53(6):3528-3539. doi: 10.1007/s12035-015-9231-1. Epub 2015 Jun 23.