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

Liao, Chih Kai; Fang, Kuan; Chai, Kitman; Wu, Chin Hsien; Ho, Chia Hsin; Yang, Chu-Sing; Tzeng, Shun Fen

doi:10.1007/s12035-015-9231-1

Cited by 12 publications

(9 citation statements)

References 34 publications

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“…1. B cell lines: Naïve B cells can differentiate into antibody-secreting plasma cells after being stimulated by antigen (Liao et al, 2016). Our study found that naïve B cell was a significant decrease in gliomas, meanwhile, the plasma cells were significant increased.…”

Section: Discussionmentioning

confidence: 66%

High expression of stromal signatures correlated with macrophage infiltration, angiogenesis and poor prognosis in glioma microenvironment

Tian

2020

PeerJ

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Glioma is one of the most fatal tumors in central nervous system. Previous studies gradually revealed the association between tumor microenvironment and the prognosis of gliomas patients. However, the correlation between tumor-infiltrating immune cell and stromal signatures are unknown. In our study, we obtained gliomas samples from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). The landscape of tumor infiltrating immune cell subtypes in gliomas was calculated by CIBERSORT. As a result, we found high infiltration of macrophages was correlated with poor outcome (P < 0.05). Then functional enrichment analysis of high/low macrophage-infiltrating groups was performed by GSEA. The results showed three gene sets includes 102 core genes about angiogenesis were detected in high macrophage-infiltrating group. Next, we constructed PPI network and analyzed prognostic value of 102 core genes. We found that five stromal signatures indicated poor prognosis which including HSPG2, FOXF1, KDR, COL3A1, SRPX2 (P < 0.05). Five stromal signatures were adopted to construct a classifier. The classifier showed powerful predictive ability (AUC = 0.748). Patients with a high risk score showed poor survival. Finally, we validated this classifier in TCGA and the result was consistent with CGGA. Our investigation of tumor microenvironment in gliomas may stimulate the new strategy in immunotherapy. Five stromal signature correlated with poor prognosis also provide a strong predator of gliomas patient outcome.

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Section: Discussionmentioning

confidence: 66%

High expression of stromal signatures correlated with macrophage infiltration, angiogenesis and poor prognosis in glioma microenvironment

Tian

2020

PeerJ

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“…Based on our previous findings that Bcl11b-KD reduced the expression of stemness-related genes (Sox2 and Bmi1) in glioma cells ( Liao et al, 2016 ), we also examined the expression of stemness-related genes in the scramble and Bcl11b-KD cultures. As shown in Figure 2 , the expression of Sox2 – but not of Bmi1 – was reduced in Bcl11b-KD GPCs compared to that detected in the scramble culture.…”

Section: Resultsmentioning

confidence: 99%

“…Bcl11b has been reported to act as a transcriptional repressor to silence the expression of p21 ( Cherrier et al, 2009 ). Our previous study using human and rat glioma cells also showed that p21 expression was upregulated after the downregulation of Bcl11b expression in glioma cell lines, suggesting that Bcl11b is an important regulator for glioma cell expansion through the repression of p21 action ( Liao et al, 2016 ). The results from the present study showing that the proliferation of GPCs in GM was suppressed after Bcl11b-KD along with the upregulation of p21, also indicate that Bcl11b is involved in the maintenance of GPC stemness via the repression of p21 expression.…”

Section: Discussionmentioning

confidence: 97%

“…Previously, we found that the constructs of lentiviral vectors made in Biosettia (San Diego, CA, United States) were highly efficient in the inhibition of Bcl11b (NM_001277287) in rat glioma cells ( Liao et al, 2016 ). Thus, we used the same lentiviral vector constructs for this study: pLV-mU6-EF1a-GFP-Puro-scramble (lenti-ctrl); and, pLV-mU6-EF1a-GFP-Puro-shBcl11b-916 (lenti-shBcl11b).…”

Section: Methodsmentioning

confidence: 99%

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Function of B-Cell CLL/Lymphoma 11B in Glial Progenitor Proliferation and Oligodendrocyte Maturation

Wang

Sun

Fang

et al. 2018

Front. Mol. Neurosci.

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B-cell CLL/lymphoma 11B (Bcl11b) – a C2H2 zinc finger transcriptional factor – is known to regulate neuronal differentiation and function in the development of the central nervous system (CNS). Although its expression is reduced during oligodendrocyte (OLG) differentiation, its biological role in OLGs remains unknown. In this study, we found that the downregulation of Bcl11b gene expression in glial progenitor cells (GPCs) by lentivirus-mediated gene knockdown (KD) causes a reduction in cell proliferation with inhibited expression of stemness-related genes, while increasing the expression of cell cyclin regulator p21. In contrast, OLG specific transcription factors (Olig1) and OLG cell markers, including myelin proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG), were upregulated in Bcl11b-KD GPCs. Chromatin immunoprecipitation (ChIP) analysis indicated that Bcl11b bound to the promoters of Olig1 and PLP, suggesting that Bcl11b could act as a repressor for Olig1 and PLP, similar to its action on p21. An increase in the number of GC+- or PLP+- OLGs derived from Bcl11b-KD GPCs or OLG precursor cells was also observed. Moreover, myelin basic protein (MBP) expression in OLGs derived from Bcl11b-KD GPCs was enhanced in hippocampal neuron co-cultures and in cerebellar brain-slice cultures. The in vivo study using a lysolecithin-induced demyelinating animal model also indicated that larger amounts of MBP+-OLGs and PLP+-OLGs derived from implanted Bcl11b-KD GPCs were present at the lesioned site of the white matter than in the scramble group. Taken together, our results provide insight into the functional role of Bcl11b in the negative regulation of GPC differentiation through the repression of OLG differentiation-associated genes.

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“…A recent study revealed BCL11B as a key regulator of T-cell differentiation and maturation 30 . Attenuation of BCL11B activity also greatly enhanced β-catenin signaling, indicating a repressive effect of BCL11B in the carcinogenesis of colorectal cancers 22,31. However, it was also reported that enriched BCL11B expression in highly tumorigenic glioma cells promoted cancer cell growth by regulating the expression of stemness-associated genes (SOX2 and BMI1) 32 . Furthermore, high BCL11B expression was necessary for mammary epithelial cells to maintain quiescence 33 .…”

Section: Discussionmentioning

confidence: 99%

BCL11B suppresses tumor progression and stem cell traits in hepatocellular carcinoma by restoring p53 signaling activity

et al. 2020

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Accumulating evidence indicates that hepatocellular carcinoma (HCC) tumorigenesis, recurrence, metastasis, and therapeutic resistance are strongly associated with liver cancer stem cells (CSCs), a rare subpopulation of highly tumorigenic cells with self-renewal capacity and differentiation potential. Previous studies identified B cell leukemia/lymphoma-11b (BCL11B) as a novel tumor suppressor with impressive capacity to restrain CSC traits. However, the implications of BCL11B in HCC remain unclear. In this study, we found that low BCL11B expression was an independent indicator for shorter overall survival (OS) and time to recurrence (TTR) for HCC patients with surgical resection. In vitro and in vivo experiments confirmed BCL11B as a tumor suppressor in HCC with inhibitory effects on proliferation, cell cycle progression, apoptosis, and mobility. Furthermore, BCL11B could suppress CSC traits, as evidenced by dramatically decreased tumor spheroid formation, self-renewal potential and drug resistance. A Cignal Finder Array and dual-luciferase activity reporter assays revealed that BCL11B could activate the transcription of P73 via an E2F1-dependent manner. Thus, we concluded that BCL11B is a strong suppressor of retaining CSC traits in HCC. Ectopic expression of BCL11B might be a promising strategy for anti-HCC treatment with the potential to cure HBV-related HCC regardless of P53 mutation status.

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

Cited by 12 publications

References 34 publications

High expression of stromal signatures correlated with macrophage infiltration, angiogenesis and poor prognosis in glioma microenvironment

High expression of stromal signatures correlated with macrophage infiltration, angiogenesis and poor prognosis in glioma microenvironment

Function of B-Cell CLL/Lymphoma 11B in Glial Progenitor Proliferation and Oligodendrocyte Maturation

BCL11B suppresses tumor progression and stem cell traits in hepatocellular carcinoma by restoring p53 signaling activity

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