Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The nuclear receptor TLX (NR2E1) inhibits growth and progression of triple-negative breast cancer

ABSTRACT: Development of targeted therapies will be a critical step towards reducing the mortality associated with triple-negative breast cancer (TNBC). To achieve this, we searched for targets that met three criteria: (1) pharmacologically targetable, (2) expressed in TNBC, and (3) expression is prognostic in TNBC patients. Since nuclear receptors have a well-defined ligand-binding domain and are thus highly amenable to small-molecule intervention, we focused on this class of protein. Our analysis identified TLX (NR2E1) as a candidate. RNA-Seq analysis revealed that TLX reduced the expression of genes implicated in the pro-proliferative KRAS signaling pathway as well as epithelial-mesenchymal transition (EMT), a cellular program known to drive metastatic progression. Indeed, TLX overexpression significantly decreased cell proliferation, migration and invasion, and robustly decreased the metastatic capacity of TNBC cells in murine models. Taken together, our work indicates that TLX retards the progression of TNBC. Several ligands have been shown to regulate the transcriptional activity of TLX, providing a framework for the future development of this receptor for therapeutic intervention.

ORGANISM(S): Homo sapiens

PROVIDER: GSE196105 | GEO | 2022/07/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Tlx (nr2e1)-dependent gene expression in adult neural stem cells

Project description:Tlx (nr2e1) is an orphan nuclear receptor that is highly expressed in proliferating neural stem cells (NSCs) in the adult mouse forebrain. The goal was to identify Tlx-regulated genes in this specific cell population. Two populations of Tlx-positive neural stem cells were isolated from 2-month-old male mice based on a LacZ marker that was knocked into the Tlx locus. The first population, Tlx(f/Z;CreER), contains a floxed allele of Tlx (f), the LacZ marker (Z), and a CreER fusion transgene. Addition of tamoxifen (4OH-tamoxifen) into this NSC population leads to Cre-mediated deletion of the floxed allele of Tlx. The second NSC population, Tlx(f/Z), does not contain a CreER transgene; thus it does not respond to tamoxifen treatment and was used as a control. Keywords: Nuclear receptor-dependent gene expression

2008-12-01 | GSE9981 | GEO

Transcription profiling of mouse Tlx-positive neural stem cells isolated from 2-month-old male to investigate Tlx (nr2e1)-dependent gene expression in adult neural stem cells

Project description:Tlx (nr2e1) is an orphan nuclear receptor that is highly expressed in proliferating neural stem cells (NSCs) in the adult mouse forebrain. The goal was to identify Tlx-regulated genes in this specific cell population. Two populations of Tlx-positive neural stem cells were isolated from 2-month-old male mice based on a LacZ marker that was knocked into the Tlx locus. The first population, Tlx(f/Z;CreER), contains a floxed allele of Tlx (f), the LacZ marker (Z), and a CreER fusion transgene. Addition of tamoxifen (4OH-tamoxifen) into this NSC population leads to Cre-mediated deletion of the floxed allele of Tlx. The second NSC population, Tlx(f/Z), does not contain a CreER transgene; thus it does not respond to tamoxifen treatment and was used as a control. Experiment Overall Design: Total RNA samples from two biological replicates were collected at 36 hr or at 60 hr after tamoxifen or vehicle treatment. Total of 16 samples were used to analyze the global gene expression changes using Affymetrix chips.

2009-01-13 | E-GEOD-9981 | biostudies-arrayexpress

Ectopic TLX expression skews lineage commitment toward a myeloid fate and promotes an inflammatory phenotype

Project description:We previously showed that the orphan nuclear hormone receptor, TLX (also known as NR2E1), selectively modifies the output of IFN-gamma-driven, STAT1-dependent gene expression. Since IFN-gamma and STAT1 are also known to regulate myeloid cell development and function, we tested whether ectopic expression of TLX or COUPTF2 (a closely related orphan nuclear receptor) might influence hematopoietic differentiation. Indeed, TLX promotes lineage commitment toward myeloid development and suppresses erythropoiesis, phenocopying IFN-gamma treatment. Moreover, TLX expression in our assay is sufficient to activate a proinflammatory transcriptional program with two hallmarks: differential regulation of STAT1-dependent genes, and suppression of an anti-inflammatory program in favor of a fatty acid signature – a process known to be essential for cellular remodeling during macrophage maturation and phagocytosis. These results demonstrate an important role for a new nuclear hormone receptor in STAT1 signaling, and link TLX to myeloid lineage commitment and function.

2016-09-21 | GSE87126 | GEO

The nuclear receptor TLX (NR2E1) inhibits growth and progression of triple-negative breast cancer

Project description:The nuclear receptor TLX (NR2E1) inhibits growth and progression of triple-negative breast cancer

| PRJNA803306 | ENA

Expression data from glioblastoma stem cells

Project description:TLX (NR2E1), as an orphan nuclear receptor, plays a critical role in growth, self-renewal, and tumorigenesis of glioblastoma stem cells. We used microarrays to investigate the global gene expression regulated by TLX and identified downstream targets of TLX in glioblastoma stem cells. We further investigated the global gene expression regulated by TET3, a downstream target of TLX, to identified downstream targets of TLX-TET3 axis in glioblastoma stem cells.

2016-02-01 | GSE75945 | GEO

Genome-wide analysis of the function of Tlx in regulating mouse brain glioma gene expression

Project description:Analysis of the function of Tlx in regulating brain tumor stem cells (BTSCs) at the gene expression level. Based on our knowledge, we know that Tlx is specifically expressed in the neural stem cells in mouse brain. It also functionally regulates neurogenesis during the postnatal stages. The hypothesis tested in the present study is that Tlx influences the maintenance and progression of mouse brain gliomas through regulating the self-renewal of BTSCs and it is also a specific marker of brain tumor stem cells (BTSCs). Results provide important information about the function of Tlx in brain gliomas. Brain gliomas were initiated from the Nestin-CreERT2;Tlx flox/flox;Nestin-Tva transgenic mouse line. After 2.5 weeks, when the brain gliomas were fully developed, tamoxifen was administered through intraperitoneal injection. Tlx was knocked-out from the Cre-expressing littermates, but the littermates without Cre expression maintained intact Tlx function. Then, total RNA was obtained from mouse brain gliomas with severe neurological symptoms from the Tlx knockout and Tlx intact groups.

2013-04-17 | E-GEOD-46125 | biostudies-arrayexpress

Genome-wide analysis of the function of Tlx in regulating mouse brain glioma gene expression

2013-04-17 | GSE46125 | GEO

Nuclear orphan receptor TLX affects gene expression in pancreatic beta cells

Project description:Using Illumina’s digital gene expression (DGE) system, we investigated the transcriptional response to TLX overexpression in beta cells. Finally, an average of 13,791,918 and 12,476,623 reads of high quality clean tags were obtained from control and TLX-overexpressing beta cells, respectively. Results reveals that overexpression of TLX resulted in suppression of 176 genes by ≥50%, and also results in ≥2-fold upregulation of 49 genes.

2015-03-06 | GSE66551 | GEO

Nuclear orphan receptor TLX affects gene expression in pancreatic beta cells

Project description:Using Illumina’s digital gene expression (DGE) system, we investigated the transcriptional response to TLX overexpression in beta cells. Finally, an average of 13,791,918 and 12,476,623 reads of high quality clean tags were obtained from control and TLX-overexpressing beta cells, respectively. Results reveals that overexpression of TLX resulted in suppression of 176 genes by ?50%, and also results in ?2-fold upregulation of 49 genes. Expression profiling of stable TLX overexpressing MIN6 cells and control cells by high throughput sequencing

2015-03-06 | E-GEOD-66551 | biostudies-arrayexpress

Tumorigenic effects of TLX over-expression in HEK 293T cells

Project description:Transcriptomic profiling to investigate the effect of TLX overexpression with an inducible vector system in the HEK 293T cell line

2021-01-21 | GSE120893 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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