YAP/TAZ-dependent expression of lncRNAs [A549]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA856882 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20046837.fastq.gz | Fastqsanger.gz | |||
| SRR20046838.fastq.gz | Fastqsanger.gz | |||
| SRR20046839.fastq.gz | Fastqsanger.gz | |||
| SRR20046840.fastq.gz | Fastqsanger.gz | |||
| SRR20046841.fastq.gz | Fastqsanger.gz |
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Project description:YAP/TAZ-dependent expression of lncRNAs
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Project description:Body fluids from cancer patients are informative regarding disease conditions in tumor tissues. Thus, biomarkers detected by liquid biopsy can guide clinicians in designing personalized therapies and may serve as a proxy for treatment success. However, biomarkers that predict the existence of druggable target structures cannot be reliably defined in blood samples due to genetic tumor heterogeneity and presence of molecules from non-tumorous cells. To test the applicability of RNA signatures as liquid biopsy biomarkers, expression data from hepatocellular carcinoma (HCC) cells after inhibition of Hippo pathway effectors is investigated. We show that the oncogene yes-associated protein (YAP) transcriptionally controls a panel of long non-coding RNAs (lncRNAs), which support HCC progression via tumor cell-intrinsic mechanisms. These lncRNAs are detectable and overexpressed in YAPS127A transgenic mouse livers as well as in a subgroup of human HCC tissue and serum samples. Using a machine learning algorithm, a 4 gene lncRNA signature is defined that correlates with the nuclear abundance of YAP in HCC tissues (CYTOR, SNHG1, SNHG17, MIR4435-2HG). Importantly, YAP accumulation in human HCCs is significantly associated with lncRNA signature serum abundance in two independent patient cohorts. Evaluation of expression data and confirmatory experiments illustrate that the lncRNA signature is a robust predictor for YAP activity in other tumor types such as lung adenocarcinoma. Liquid biopsy-based detection of lncRNAs in cancer patients is informative for the activity of transcriptional regulators and can serve as diagnostic tool that guides clinicians in the design of targeted therapies.
2023-03-15 | GSE207723 | GEO
Project description:The optic vesicle comprises a pool of bi-potential progenitor cells from which the retinal pigment epithelium (RPE) and neural retina fates segregate during ocular morphogenesis. Several transcription factors and signaling pathways have been shown to be important for RPE maintenance and differentiation, but an understanding of the initial fate specification and determination of this ocular cell type is lacking. We show that Yap/Taz-Tead activity is necessary and sufficient for optic vesicle progenitors to adopt RPE identity in zebrafish. A Teadresponsive transgene is expressed within the domain of the optic cup from which RPE arises, and Yap immunoreactivity localizes to the nuclei of prospective RPE cells. yap (yap1) mutants lack a subset of RPE cells and/or exhibit coloboma. Loss of RPE in yap mutants is exacerbated in combination with taz (wwtr1) mutant alleles such that, when Yap and Taz are both absent, optic vesicle progenitor cells completely lose their ability to form RPE. The mechanism of Yap dependent RPE cell type determination is reliant on both nuclear localization of Yap and interaction with a Tead co-factor. In contrast to loss of Yap and Taz, overexpression of either protein within optic vesicle progenitors leads to ectopic pigmentation in a dosagedependent manner. Overall, this study identifies Yap and Taz as key early regulators of RPE genesis and provides a mechanistic framework for understanding the congenital ocular defects of Sveinsson’s chorioretinal atrophy and congenital retinal coloboma. 60 pooled eyes from 36 hpf wild type or vsx2:Gal4/dsRed:14xUAS:YapS87A embryos were pooled for one sample. Three wild type and three vsx2:Gal4/dsRed:14xUAS:YapS87A pools were analyzed for RNA.
2015-08-06 | E-GEOD-71681 | biostudies-arrayexpress
Project description:The Hippo pathway effectors yes-associated protein (YAP) and WW domain containing transcription regulator 1 (TAZ/WWTR1) support tumor initiation and progression in various cancer types. However, to which extent YAP and TAZ cooperatively contribute to cholangiocarcinoma (CCA) development and progression is poorly understood. Our immunohistochemical studies showed that YAP and TAZ were expressed in different CCA subtypes. However, nuclear co-expression was not frequently detected. RNAinterference (RNAi) experiments illustrated that YAP and TAZ supported CCA cell viability. Comprehensive expression profiling of HUCCT-1 cells after combined silencing of YAP/TAZ revealed a potential impact on chromosomal instability.
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Project description:Genes regulated by TAZ or YAP in A549 cell
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Project description:Body fluids from cancer patients are informative regarding disease conditions in tumor tissues. Thus, biomarkers detected by liquid biopsy can guide clinicians in designing personalized therapies and may serve as a proxy for treatment success. However, biomarkers that predict the existence of druggable target structures cannot be reliably defined in blood samples due to genetic tumor heterogeneity and presence of molecules from non-tumorous cells. To test the applicability of RNA signatures as liquid biopsy biomarkers, expression data from hepatocellular carcinoma (HCC) cells after inhibition of Hippo pathway effectors is investigated. We show that the oncogene yes-associated protein (YAP) transcriptionally controls a panel of long non-coding RNAs (lncRNAs), which support HCC progression via tumor cell-intrinsic mechanisms. These lncRNAs are detectable and overexpressed in YAPS127A transgenic mouse livers as well as in a subgroup of human HCC tissue and serum samples. Using a machine learning algorithm, a 4 gene lncRNA signature is defined that correlates with the nuclear abundance of YAP in HCC tissues (CYTOR, SNHG1, SNHG17, MIR4435-2HG). Importantly, YAP accumulation in human HCCs is significantly associated with lncRNA signature serum abundance in two independent patient cohorts. Evaluation of expression data and confirmatory experiments illustrate that the lncRNA signature is a robust predictor for YAP activity in other tumor types such as lung adenocarcinoma. Liquid biopsy-based detection of lncRNAs in cancer patients is informative for the activity of transcriptional regulators and can serve as diagnostic tool that guides clinicians in the design of targeted therapies.
2023-03-15 | GSE207722 | GEO
Project description:YAP/TAZ-dependent transcriptome in cholangiocarcinoma cells
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Project description:Angiogenesis, the process by which endothelial cells (ECs) form new blood vessels from existing ones, is intimately linked to the tissue's metabolic milieu and often occurs at nutrient-deficient sites. However, ECs rely on sufficient metabolic resources to support growth and proliferation. How endothelial nutrient acquisition and usage are regulated is unknown. Here we show that these processes are dictated by YAP/TAZ-TEAD – a transcriptional module whose function is highly responsive to changes in the tissue environment. ECs lacking YAP/TAZ or their transcriptional partners, TEAD1, 2, and 4 fail to divide, resulting in stunted vascular growth in mice. Conversely, activation of TAZ, the more abundant paralogue in ECs, boosts proliferation, leading to vascular hyperplasia. We find that YAP/TAZ promote angiogenesis by fueling nutrient mTORC1 signaling. By orchestrating the transcription of a repertoire of cell-surface transporters, YAP/TAZ-TEAD stimulate the import of amino acids and other essential nutrients, thereby enabling mTORC1 pathway activation. Dissociating mTORC1 from these nutrient inputs – elicited by the loss of Rag GTPases – inhibits mTORC1 activity and prevents YAP/TAZ-dependent vascular growth. These findings define a pivotal role for YAP/TAZ-TEAD in steering endothelial mTORC1 and illustrate the essentiality of coordinated nutrient fluxes in the vasculature.
2022-05-08 | PXD026872 | Pride
Project description:The Hippo pathway plays a crucial in organ size control during development and tissue homeostasis in adult life. To examine a role for Hippo signaling in the intestinal epithelium, we analyzed gene expression patterns in the mouse intestinal epithelilum transfected with siRNAs or expression plasmids for shRNAs targeting the Hippo pathway effectors, YAP and TAZ. We performed two independent series of experiments (siGFP (n=3) vs siYAP/siTAZ (n=3), and shLacZ (n=1) vs shYAP/shTAZ (n=1)). Control siRNA (siGFP), YAP/TAZ siRNAs, or expression plasmids for control shRNA (shLacZ) or YAP/TAZ shRNAs were introduced into the mouse intestinal epithelium by the newly-developed in vivo transfection method. Four days after transfection, intestinal epithelial cells were isolated from the tissues and total RNA was extracted.
2014-07-18 | E-GEOD-45155 | biostudies-arrayexpress