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LITAF, a BCL6 target gene, regulates autophagy in mature B-cell lymphomas

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE42204 | GEO | 2012/11/10

SECONDARY ACCESSION(S): PRJNA179282

REPOSITORIES: GEO

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LITAF, a BCL6 target gene, regulates autophagy in mature B-cell lymphomas.

Project description:We have previously reported that LITAF is silenced by promoter hypermethylation in germinal centre-derived B-cell lymphomas, but beyond these data the regulation and function of lipopolysaccharide-induced tumour necrosis factor (TNF) factor (LITAF) in B cells are unknown. Gene expression and immunohistochemical studies revealed that LITAF and BCL6 show opposite expression in tonsil B-cell subpopulations and B-cell lymphomas, suggesting that BCL6 may regulate LITAF expression. Accordingly, BCL6 silencing increased LITAF expression, and chromatin immunoprecipitation and luciferase reporter assays demonstrated a direct transcriptional repression of LITAF by BCL6. Gain- and loss-of-function experiments in different B-cell lymphoma cell lines revealed that, in contrast to its function in monocytes, LITAF does not induce lipopolysaccharide-mediated TNF secretion in B cells. However, gene expression microarrays defined a LITAF-related transcriptional signature containing genes regulating autophagy, including MAP1LC3B (LC3B). In addition, immunofluorescence analysis co-localized LITAF with autophagosomes, further suggesting a possible role in autophagy modulation. Accordingly, ectopic LITAF expression in B-cell lymphoma cells enhanced autophagy responses to starvation, which were impaired upon LITAF silencing. Our results indicate that the BCL6-mediated transcriptional repression of LITAF may inhibit autophagy in B cells during the germinal centre reaction, and suggest that the constitutive repression of autophagy responses in BCL6-driven lymphomas may contribute to lymphomagenesis.

| S-EPMC4111142 | biostudies-literature

LITAF, a BCL6 target gene, regulates autophagy in mature B-cell lymphomas

Project description:This SuperSeries is composed of the following subset Series: GSE42174: Global expression analysis of DLBCL cell lines with LITAF over-expression or silencing GSE42203: Global expression analysis of DLBCL and SMZL cell lines Refer to individual Series

2012-11-10 | E-GEOD-42204 | biostudies-arrayexpress

A recurrent 11q aberration pattern characterizes a subset of MYC-negative mature aggressive B-cell lymphomas resembling Burkitt lymphoma