Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TGFb treated EpRAS cells undergoing hysteretic vs non-hysteretic EMT gene expression analysis.

ABSTRACT: EpRAS cells undergo EMT transition through hysteresis showing bistability of the system. The hysteresis transition is controlled by the negative feedback loop between miR-200s and Zeb1. Disruption of the feedback loop through the deletion of Z-box2 in the miR-200s cluster-2 promoter region changes the transition to unimodal without hysteresis. To determine the consequence of cells undergoing through hysteresis or unimodal transitions of EMT, herein we determined the transcriptomic profiles of EpRAS wild type and EpRAS-delZbox2 mutant cells, (designated as EpRAS-C2-2). To induce EMT, the cells were treated with 100pM TGFbeta for 3 days. Mock PBS treatment is used as control.

ORGANISM(S): Mus musculus

PROVIDER: GSE106533 | GEO | 2018/11/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Dynamics of chromatin accessibility during TGF-beta-induced EMT of Ras-transformed mammary gland epithelial cells

Project description:This SuperSeries is composed of the SubSeries listed below. Epithelial-mesenchymal transition (EMT) is induced by transforming growth factor (TGF)-beta stimulation and facilitates tumor progression. We here performed global mapping of accessible chromatin in the mouse mammary gland epithelial EpH4 cell line and its Ras-transformed derivative (EpRas) using formaldehyde-assisted isolation of regulatory element (FAIRE)-sequencing (seq). We also searched for differentially expressed transcription factors by RNA-seq and found that Etv4, an ETS family oncogenic transcription factor, was strongly expressed in EpRas cells. Moreover, chromatin immunoprecipitation (ChIP)-seq showed that Etv4 bound to more than one-third of the accessible chromatin regions in EpRas cells treated with TGF-beta. We found by gene ontology analysis that genes encoding extracellular proteins are the most strongly down-regulated genes by Etv4 and Etv5 siRNAs. These findings suggest a mechanism of transcriptional regulation during TGF-beta-induced EMT that involves alterations of accessible chromatin.

2017-04-10 | GSE69387 | GEO

Overexpression of miR-200s in murine ovarian cancer cells (ID8 and 28-2)

Project description:Little is known about the role of miR-200s in the progression of ovarian cancer. In this study we overexpressed the miR-200c/141 cluster, the miR-200b/200a/429 cluster, or both clusters in two different murine ovarian cancer cell lines (ID8 and 28-2). As co-oeverexpression of both clusters provided the best miR-200 overexpression, we evaluated ID8 and 28-2 cells overexpressing both miR-200 clusters (ID8-200f and 28-2-200f) compared to empty vector control cells (ID8EV and 28-2EV). ID8-200f and 28-2-200f cells showed increased expression of several mesenchymal genes, decreased proliferation, decreased invasion and increased apoptosis compared to their respective controls. RNA sequencing of ID8EV, ID8-200f, 28-2EV and 28-2-200f cells revealed that overexpression of miR-200s primary regulated genes involved in epithelial mesenchymal transition EMT) and gene implicated in migration. Therefore, our work suggests that miR-200s can inhibit characteristics associated ovarian cancer progression (increased proliferation and invasion and promotion of EMT).

2024-07-03 | GSE250195 | GEO

Histone modification analysis in TGFbeta/TNFalpha treated A549 spheroid cultures

Project description:We studied the extent of chromatin remodeling in an in-vitro model of the epithelial-mesenchymal transition (EMT). EMT is induced in spheroid cultures (3D) using simultaneously two cytokines: TGFbeta and TNFalpha. The epithelial-mesenchymal transition (EMT) is a cellular de-differentiation process that has been implicated in cancer progression and metastasis. Increasing evidence suggests that EMT is regulated and established by epigenetic reprogramming, however a systems-level mechanism describing how chromatin remodeling contributes to the phenotypic switch is not known. We have generated genome-wide maps of 18 histone modifications/variants and variants in both the epithelial and mesenchymal states and quantified patterns of epigenetic changes at gene and enhancer loci. Clusters of these patterns reveal that EMT-related genes and their proximal enhancers are regulated through coordinated patterns of chromatin activation and repression at both gene and enhancer loci. At the cellular level, the remodeling of gene loci translates into a modular protein interaction network that recapitulates EMT-related signaling. Moreover, differentially activated or repressed enhancers are associated with two non-overlapping sets of transcription factors. We propose a chromatin-mediated regulatory feedback loop model where the NFkappaB and AP-1 transcription factors (TFs) bind activated enhancers, that regulate EMT-related genes, which in turn activate signaling pathways upstream of these TFs.

2013-09-12 | E-GEOD-42374 | biostudies-arrayexpress

LncRNA LETS1 promotes TGF--induced EMT and cancer progression

Project description:Transforming growth factor- (TGF-) signaling is a critical driver of epithelial–mesenchymal transition (EMT) and cancer progression. However, the regulatory roles of long non-coding RNAs (lncRNAs) in TGF--induced EMT and cancer progression are not well understood. Here, we identified an unannotated nuclear lncRNA LETS1 (LncRNA Enforcing TGF- Signaling 1) as a novel TGF-/SMAD target gene. Loss of LETS1 attenuates TGF--induced EMT, migration and extravasation in breast and lung cancer cells. LETS1 potentiates TGF-/SMAD signaling by stabilizing cell surface TGF- type I receptor (TRI) and thereby forms a positive feedback loop. Mechanistically, LETS1 inhibits TRI polyubiquitination by inducing the orphan nuclear receptor 4A1 (NR4A1) expression, a critical determinant of a destruction complex for inhibitory SMAD7. An unbiased interactome analysis identified the Nuclear Factor of Activated T Cells (NFAT5) as a protein partner of LETS1 to mediate activation of NR4A1 promoter. Overall, our findings characterize LETS1 as an EMT-promoting lncRNA and elucidate the mechanism by which nuclear LETS1 potentiates TGF- receptor signaling.

2023-07-31 | PXD037401 | Pride

Noncanonical post-transcriptional feedback between microRNA and messenger RNA enables bistability and governs robust cell fate decisions

Project description:Positive feedback driven by transcriptional regulation has long been considered a key mechanism underlying cell lineage segregation during embryogenesis. Using the developing spinal cord as a paradigm, we found that canonical, transcription-driven feedback cannot explain robust lineage segregation of motor neuron subtypes marked by two cardinal factors, Hoxa5 and Hoxc8. We propose a feedback mechanism involving elementary microRNA-mRNA reaction circuits that differ from known feedback loop-like structures. Strikingly, we show that a wide range of biologically-plausible post-transcriptional regulatory parameters are sufficient to generate bistable switches, a hallmark of positive feedback. Through mathematical analysis, we explain intuitively the hidden source of this feedback. Using embryonic stem cell differentiation and mouse genetics, we corroborate that microRNA-mRNA circuits govern tissue boundaries and hysteresis upon motor neuron differentiation with respect to transient morphogen signals. Our findings reveal a previously underappreciated feedback mechanism that may have widespread functions in cell fate decisions and tissue patterning.

2021-04-14 | GSE156023 | GEO

RNA-sequencing of EpH4 and EpRas cells treated with Etv4 and Etv5 siRNAs and/or TGF-beta.

Project description:We performed RNA-seq analysis in mouse mammary gland epithelial EpH4 cell line and its Ras-transformed derivative (EpRas) to analyze the mechanisms of transcriptional regulation during TGF-beta-induced EMT.

2017-04-10 | GSE69363 | GEO

Analysis of gene expression changes during long-term induction of EMT in EpRas tumor cells by TGF-b1.

Project description:EMT is a developmental process, which can be reactivated in cancer cells. Cancer cells maintaining EMT in the circulation may have pro-metastatic properties. We used microarrays to profile EMT-related gene expression changes after 14 d of TGF-b1 treatment. EpRas cells were cultured in standard conditions either in the presence of absence of recombinant TGF-b1 (2 ng/ml) for 14 d. After this period, RNA was isolated from triplicate wells of treated and non-treated cells, and hybridized on Affymetrix microarrays.

2014-09-01 | E-GEOD-59922 | biostudies-arrayexpress

KLHL23 Regulates a Novel Positive-Feedback Signaling Loop of EMT Maintaining the Mesenchymal State of Cancer Cells during Metastasis

Project description:Epithelial-mesenchymal transition (EMT) is initiated and regulated by a transcriptional reprogramming in response to microenvironmental cues. How cancer cells overcome the lack of such cues during the metastatic journey remains unclear. Here we report a novel positive-feedback loop of EMT that maintains the mesenchymal traits of cancer cells during metastasis. Using subgenome-wide screening, we identified KLHL23 as a tumor invasion suppressor, which binds to actin and suppresses actin-filament formation. Silencing or ectopic expression of KLHL23 induces EMT or MET (mesenchymal-epithelial transition), respectively, through its action on actin dynamics. Increased actin-dynamics by silencing KLHL23 or treatment with F-actin disruptors or inducers enhances the EMT transcriptional reprogramming via the induction of ROS, HIF-1a, HIF-2a and NOTCH signalling pathways in cancer cells under stress or ongoing EMT. Downregulation of KLHL23 is found in human liver and pancreatic cancers and associated with tumor metastasis and poor prognosis.

2016-11-01 | GSE74996 | GEO

FAIRE-seq analysis of Ras transformed mouse mammary gland epithelial cells transfected with Etv4 and Etv5 siRNAs and stimulated with TGF-beta.

Project description:We performed global mapping of accessible chromatin in mouse mammary gland epithelial EpH4 cell line and its Ras-transformed derivative (EpRas) using formaldehyde-assisted isolation of regulatory element (FAIRE)-sequencing (seq) to analyze the mechanisms of transcriptional regulation during TGF-beta-induced EMT.

2017-04-10 | GSE94977 | GEO

Dynamics of chromatin accessibility during TGF-beta-induced EMT of Ras-transformed mammary gland epithelial cells [FAIRE-Seq]

2017-04-10 | GSE69364 | GEO