A systematic analysis of the time series gene expression in TGF-beta induced EMT by Next-generation sequencing
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE69667 | GEO | 2016/03/02
SECONDARY ACCESSION(S): PRJNA286131
REPOSITORIES: GEO
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Project description:The goal of this study is to characterize time course gene expression profiles during TGF-beta induced EMT. In particular, we aim to identify and characterize master transcription factors regulate the transition into partial-EMT state. A time series mRNA profile in A549 cells is generated from TGF-beta induced EMT samples during 0h,6h,12h,24h,36h,48h,72h and 96h by deep sequencing, in duplicate, using Illumina HiSeq 2500
2016-03-02 | E-GEOD-69667 | biostudies-arrayexpress
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.
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Project description:The purpose of this study is to determine the changes in gene expression by a human retinal pigment epithelium (RPE) cell line (ARPE-19) in response to combination treatment of TGF and TNF, which induces phenotypic changes in vitro that mimic the EMT (Epithelial-to-Mesenchymal Transition). For this purpose, total RNA was extracted from TGF and TNF-treated ARPE-19 cells and differential gene expression between each time point (0, 1, 6, 16, 24, 42, and 60 hours) was determined using genechip arrays (Affymetrix, Human Genome U133). Keywords: time course
2009-08-26 | GSE12548 | GEO
Project description:Aberrant epithelial-mesenchymal transition (EMT) is involved in pathological processes including fibrotic disorders and cancer invasion and metastasis. Alterations of the cell-extracellular matrix (ECM) interaction also contribute to those pathological settings. However, the functional interplay between EMT and cell-ECM interaction is poorly understood. Here, we show that tumor necrosis factor (TNF)-alpha, a potent mediator of inflammation, induces EMT-associated fibrosis in retinal pigment epithelial cells, and that this is regulated by hyaluronan (HA)-CD44-Moesin interaction. TNF-alpha elicits both HA synthesis and Moesin phosphorylation through protein kinase C activation, promoting binding of CD44 to the newly synthesized HA. The HA-CD44-Moesin interaction leads to cell-cell dissociation through actin remodeling and increased cellular motility associated with mesenchymal phenotype. Furthermore, we established an in vivo model of TNF-alpha-induced fibrosis in the mouse eye, and the ocular fibrosis was completely suppressed in CD44-null mice. Therefore, HA production and its interaction with CD44 plays essential role in TNF-alpha-induced-EMT, and the interference of the complex formation can be a new strategy for the fibrotic disorders. ARPE19 cell lines were treated with TGF and TNF for 6 and 42 hour. Each experiment were repeated three times. But 1hour experiment was repeated two times. For this submission, total RNA was extracted from TGF- or TNF-treated ARPE-19 cells and differential gene expression between each time point (6 and 42 hours) was determined using genechip arrays (Affymetrix, Human Genome U133).
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2004-10-01 | E-MEXP-139 | biostudies-arrayexpress
Project description:Our group is interested in epithelial-to-mesenchymal transition (EMT), in particular, TGF-beta induced EMT. TGF-beta signalling has been shown to be an important factor in the induction of EMT and it has been demonstrated that adding TGF-beta to epithelial cells in culture is a convenient way to study the process of EMT. In response to TGF-beta, Smad2 and 3 are activated, and form complexes with Smad4, which then regulate transcription of target genes through interactions with other DNA binding transcription factors. In the induction of EMT, the activated Smads mediate transcriptional regulation through three families of transcription factors, resulting in repression of epithelial marker gene expression and activation of mesenchymal gene expression (Xu J, et al. 2009) <br></br> Also investigated in this study is the role of H2A.Z in EMT. H2A.Z is an evolutionary conserved and a metazoan essential histone variant of the H2A class. Mice deficient in H2A.Z die during early development but the reason for this is unknown (Faast et al. 2001). Previously, our laboratory showed that the loss of H2A.Z in Xenpous laevis impaired cell movement required for the formation of the mesoderm and neural crest (Ridgway et al. 2004). Given that mesoderm formation is critically dependent upon EMT, we therefore wondered whether H2A.Z might be a chromatin regulator of EMT. We transfected MDCK cells with a lentiviral vector to express a construct encoding an shRNA targeting canine H2A.Z as we wanted to test the hypothesis that H2A.Z is involved in the maintenance of cellular identity and that its loss might trigger de-differentiation. <br></br> In order to investigate changes in histone variant H2A.Z occupancy associated with TGF-beta induced epithelial-to-mesenchymal transition (EMT) we performed H2A.Z ChIP-Seq in untreated and TGFb-treated MDCK cells. The MDCK cell line has been extensively used as a model system for EMT because they convert fully from the epithelial to the mesenchymal state in response to TGF-beta. <br></br>Please note that RNA-seq data generated in conjunction to this ChIP-seq data set were also deposited at ArrayExpress under accession number E-MTAB-5628 ( https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-5628 ).
2017-10-23 | E-MTAB-5637 | biostudies-arrayexpress
Project description:TGF-β is a major tumor suppressor in gastrointestinal (GI) and squamous carcinomas, which exhibit frequent genetic inactivation of Smad4, a key TGF-β signaling component. Apoptosis is implicated as an important mediator of the tumor suppressive function of TGF-β, although this process remains poorly understood. To address this long-standing question, we dissected the tumor suppressive action of TGF-β in naïve pancreatic ductal adenocarcinoma (PDA) cells. Here we show that TGF-β/Smad4 signaling triggers an EMT in Kras-mutant pancreatic progenitor cells but turns this process into a trigger of apoptosis by converting the progenitor cell transcription factor Sox4 from an enforcer of epithelial progenitor identity into an activator of apoptosis. This occurs as a result of the EMT-linked repression of the endodermal master regulator Klf5, which cooperates with Sox4 to promote epithelial progenitor identity, and loss of which unmasks a latent apoptotic transcriptional program driven by Sox4. By losing Smad4, Kras-mutant PDA cells avoid this fate and instead use Sox4 as a TGF-β-dependent enforcer of the epithelial progenitor cell state. In this study, 16 RNA-Seq samples and 6 ChIP-Seq samples are included.
2016-02-24 | E-GEOD-72069 | biostudies-arrayexpress
Project description:Epithelial-to-mesenchymal transitions (EMT) play prominent roles during development, regeneration and tumor progression. EMTs are triggered by TGF-β, RAS and other signals that cooperatively induce the expression of master EMT transcription factors such as SNAIL. Here, we elucidate how the TGF-β and RAS pathways jointly trigger EMTs and tie them to broader developmental programs. We identify RAS response element binding protein 1 (RREB1) as a critical partner of TGF-β-activated SMAD transcription factors in driving SNAIL expression and EMT program in mammary gland epithelial cells.
2020-01-09 | GSE128958 | GEO
Project description:TGF-β is a major tumor suppressor in gastrointestinal (GI) and squamous carcinomas, which exhibit frequent genetic inactivation of Smad4, a key TGF-β signaling component. Apoptosis is implicated as an important mediator of the tumor suppressive function of TGF-β, although this process remains poorly understood. To address this long-standing question, we dissected the tumor suppressive action of TGF-β in naïve pancreatic ductal adenocarcinoma (PDA) cells. Here we show that TGF-β/Smad4 signaling triggers an EMT in Kras-mutant pancreatic progenitor cells but turns this process into a trigger of apoptosis by converting the progenitor cell transcription factor Sox4 from an enforcer of epithelial progenitor identity into an activator of apoptosis. This occurs as a result of the EMT-linked repression of the endodermal master regulator Klf5, which cooperates with Sox4 to promote epithelial progenitor identity, and loss of which unmasks a latent apoptotic transcriptional program driven by Sox4. By losing Smad4, Kras-mutant PDA cells avoid this fate and instead use Sox4 as a TGF-β-dependent enforcer of the epithelial progenitor cell state.
2016-02-24 | GSE72069 | GEO
Project description:Vicious circle of some key proteins is critical in the process of tumor development. Nevertheless, the mechanism of how the epigenetic modifiers are involved in was seldom reported and has not been clearly illustrated. We found the expression of lysine specific demethylase 1 (LSD1), the first identified histone lysine demethylase, is positively correlated with transforming growth factor beta 1 (TGF β1) in gastric cancer tissues and can be promoted by TGF β1 activated (p-EKR)-(NF-κB)-p300 signaling pathway, which resulted in the progression of epithelial-mesenchymal transition (EMT) in human gastric cancer cells. On the other hand, abrogation of LSD1 leads to the down regulation of TGF β1 as well as the EMT. But in benign cells, this circle was blocked by TGF β1 induced inactivation of ERK, which suggested the distinct roles of TGF β1 against LSD1 in gastric cancer cells and benign cells. This vicious cycle may illustrate a novel mechanism for EMT in gastric cancer mediate by TGF β1 and LSD1 but not in benign cells and may serve as a new strategy for the prevention of EMT for gastric cancer. Nuclear extracts prepared from MGC803 cells stably expressing Lenti-CAS9-sgRNA-puro for LSD1 or empty vector were used in immunoprecipitation reactions with antibodies against H3K4me2 and H3K9me2. Sequencing libraries were prepared using the TruSeq DNA Sample Prep Kit (Illumina) and sequencing was performed on a HiSeq2000 (Illumina).
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