Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

BCL6 Enables Cancer Cells to Evade Genotoxic Stress

ABSTRACT: BCL6 Enables Cancer Cells to Evade Genotoxic Stress

PROVIDER: PRJNA679550 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR13085030_1.fastq.gz	Fastqsanger.gz
	SRR13085030_2.fastq.gz	Fastqsanger.gz
	SRR13085031_1.fastq.gz	Fastqsanger.gz
	SRR13085031_2.fastq.gz	Fastqsanger.gz
	SRR13085032_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 36

Similar Datasets

BCL6 Enables Cancer Cells to Evade Genotoxic Stress

Project description:Genotoxic agents remain the mainstay of cancer treatment. Unfortunately, clinical benefit is often countered by a rapid adaptive response in tumors. Here we report that the proto-oncogene BCL6 is a core component conferring tumor resistance adaption. In response to genotoxic stress, BCL6 transcription was markedly promoted in cancer cells. BCL6 upregulation was positively associated with therapy resistance and poor progression-free survival in patients. Mechanistically, we discovered that treatment of the genotoxic agent etoposide led to transcriptional reprogramming of multiple proinflammatory cytokines, among which interferon-α and interferon-γ response were significantly enriched in resistant cells. Our results further revealed that the interferon/STAT1 axis that was required for the therapeutic efficacy of etoposide directly regulated BCL6 expression. Increased BCL6 consequently activated mTOR pathway through repressing the tumor suppressor PTEN to enable cancer cell survival. Importantly, targeted inhibition of BCL6 potentiated etoposide-triggered DNA damage and apoptosis in vitro and in vivo. Collectively, our findings highlight the significance of targeting previously uncharacterized interferon-mediated BCL6 pathway to conquer tolerance of cancer cells to genotoxic stress.

2021-11-19 | GSE161803 | GEO

The oncoprotein BCL6 enables solid tumor cells to evade genotoxic stress.

Project description:Genotoxic agents remain the mainstay of cancer treatment. Unfortunately, the clinical benefits are often countered by a rapid tumor adaptive response. Here, we report that the oncoprotein B cell lymphoma 6 (BCL6) is a core component that confers solid tumor adaptive resistance to genotoxic stress. Multiple genotoxic agents promoted BCL6 transactivation, which was positively correlated with a weakened therapeutic efficacy and a worse clinical outcome. Mechanistically, we discovered that treatment with the genotoxic agent etoposide led to the transcriptional reprogramming of multiple pro-inflammatory cytokines, among which the interferon-α and interferon-γ responses were substantially enriched in resistant cells. Our results further revealed that the activation of interferon/signal transducer and activator of transcription 1 axis directly upregulated BCL6 expression. The increased expression of BCL6 further repressed the tumor suppressor PTEN and consequently enabled resistant cancer cell survival. Accordingly, targeted inhibition of BCL6 remarkably enhanced etoposide-triggered DNA damage and apoptosis both in vitro and in vivo. Our findings highlight the importance of BCL6 signaling in conquering solid tumor tolerance to genotoxic stress, further establishing a rationale for a combined approach with genotoxic agents and BCL6-targeted therapy.

| S-EPMC9064299 | biostudies-literature

Cancer cells utilize self-inflicted DNA breaks to evade growth limits imposed by exogenous genotoxic stress

Project description:Cancer cells utilize self-inflicted DNA breaks to evade growth limits imposed by exogenous genotoxic stress

| PRJNA718847 | ENA

XPO1 enables adaptive regulation of mRNA export required for genotoxic stress tolerance in cancer cells

Project description:XPO1 enables adaptive regulation of mRNA export required for genotoxic stress tolerance in cancer cells

| PRJNA871300 | ENA

Cotranscriptional exon skipping in the genotoxic stress response

Project description:Pre-mRNA splicing is functionally coupled to transcription, and genotoxic stresses can enhance alternative exon inclusion by affecting elongating RNA polymerase II. We report here that various genotoxic stress inducers, including camptothecin, inhibit the interaction between EWS, an RNA polymerase II-associated factor, and YB-1, a spliceosome-associated factor. This results in the cotranscriptional skipping of several exons of the MDM2 gene encoding the main p53 ubiquitin-ligase. This reversible exon skipping participates in the timely regulation of MDM2 expression, and may contribute to the accumulation of p53 during stress exposure and its rapid shut off when stress is removed. Finally, a splicing-sensitive microarray identified numerous exons that are skipped in response to camptothecin and EWS/YB-1 depletion. These data demonstrate genotoxic stress-induced alteration of the communication between the transcriptional and splicing machineries, resulting in widespread exon skipping and playing a central role in the genotoxic stress response.

2010-05-20 | GSE21840 | GEO

Cotranscriptional exon skipping in the genotoxic stress response

2010-06-09 | E-GEOD-21840 | biostudies-arrayexpress

BCL6 evolved in vertebrates as a stress tolerance gene and is broadly used by cancer cells to adapt to stress

Project description:We have found that BCL6 is a component of the conserved stress response program regulated by HSF1. BCL6 mediates cellular adaptation to stress by repressing genes through its BTB domain. These genes fail to be repressed after stress in a murine model with point mutations in the BCL6 BTB domain that disrupt its repressor activity.

2019-11-20 | GSE69974 | GEO

The Mycobacterium tuberculosis transcriptional landscape under genotoxic stress.

Project description:The Mycobacterium tuberculosis transcriptional landscape under genotoxic stress

| PRJEB13114 | ENA

The proteomic landscape of genotoxic stress-induced micronuclei

Project description:Micronuclei (MN) are induced by various genotoxic stressors and amass nuclear- and cytoplasmic-resident proteins, priming the cell for MN-driven signalling cascades. Here, we measure the proteome of micronuclear, cytoplasmic, and nuclear fractions from human cells exposed to a panel of six genotoxins, comprehensively profiling their MN protein landscape. This dataset represents a unique resource detailing the proteomic landscape of MN, guiding mechanistic studies of MN generation and MN-associated outcomes of genotoxic stress.

2023-07-31 | MSV000092560 | MassIVE

Cancer cells utilize self-inflicted DNA breaks to evade growth limits imposed by exogenous genotoxic stress

Project description:Exposure to genotoxic challenge activates cell cycle checkpoints to prevent progression and propagation of deleterious DNA damage. We identify the activity of a nuclease, Caspase-activated DNase (CAD), in promoting G2 checkpoint control in cancer cells via the infliction of DNA breaks. To appreciate the genomic context of these breaks, we performed (genome wide ligation of 3’-hydroxy (OH) ends followed by sequencing), to map the endogenously inflicted DNA breaks following irradiation.

2022-03-28 | GSE171242 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data