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BCL6 enforces human glioblastoma growth and serves as a novel therapeutic target (expression)

ABSTRACT: This study uncovers a novel growth-promoting role of BCL6 in GBM, and provide the rationale of targeting BCL6 as a potential therapeutic approach for this deadly malignancy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE77053 | GEO | 2016/08/01

SECONDARY ACCESSION(S): PRJNA309336

REPOSITORIES: GEO

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BCL6 enforces human glioblastoma growth and serves as a novel therapeutic target (expression)

Project description:ZBTB transcription factors extensively orchestrate gene transcription during tissue development. However, their roles in glioblastoma multiforme (GBM) remain largely unexplored. Here, through integrated functional screening and expression analyses of 49 human ZBTB genes, we identify that BCL6 is required for GBM cell proliferation and is overexpressed in GBM samples. High expression of BCL6 is associated with poor overall survival of GBM patients. Genome-wide occupancy analysis and transcriptome analysis demonstrates that BCL6 is recruited to the loci of various tumor-promoting genes (e.g. MYC, FOSL1, MALAT1 and NEAT1) and maintains their expression. Pathway enrichment analysis reveals that BCL6 regulates several important cancer related pathways (e.g. TP53, ErbB and MAPK signaling pathways). BCL6 represses the expression of TP53 and its target genes, CDKN1A and CDKN1B, thereby promoting GBM cell resistance to ionizing radiation. Moreover, antibody array profiling uncovers AXL and MET are selectively activated by BCL6 in GBM. Moreover, BCL6 enhances both MEKERK and S6K-RPS6 axes as well as cap-dependent translation through the induction of AXL expression. Importantly, depletion of BCL6 or pharmacological inhibition of BCL6/NCoR complex effectively blocks GBM growth both in vitro and in vivo, and sensitizes GBM cells to EGFR inhibitors. Together, these findings uncover a novel growth-promoting role of BCL6 in GBM, and provide the rationale of targeting BCL6 as a potential therapeutic approach for this deadly malignancy. cDNA microarray analysis was performed in U87 cells transfected with either non-targeting siRNAs or BCL6 siRNAs. All experiments were carried out in duplicates.

2016-08-01 | E-GEOD-77053 | biostudies-arrayexpress

Bcl6

Project description:Rattus norvegicus Bcl6, BCL6, transcription repressor [Source:RGD Symbol;Acc:1309345], is differentially expressed in 27 experiment(s);

| ENSRNOG00000001843 | ExpressionAtlas

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Project description:Rattus norvegicus Bcl6, BCL6, transcription repressor [Source:RGD Symbol;Acc:1309345], is expressed in 5 baseline experiment(s);

| ENSRNOG00000001843 | ExpressionAtlas

BCL6

Project description:Sus scrofa BCL6, BCL6 transcription repressor [Source:VGNC Symbol;Acc:VGNC:96565], is differentially expressed in 6 experiment(s);

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BCL6

Project description:Macaca mulatta BCL6, BCL6 transcription repressor [Source:VGNC Symbol;Acc:VGNC:70036], is expressed in 3 baseline experiment(s);

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BCL6

Project description:Oryctolagus cuniculus BCL6, BCL6 transcription repressor [Source:HGNC Symbol;Acc:HGNC:1001], is expressed in 1 baseline experiment(s);

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Project description:Equus caballus BCL6, BCL6 transcription repressor [Source:VGNC Symbol;Acc:VGNC:57978], is expressed in 1 baseline experiment(s);

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