Discovery of YAP target genes with TNFa or IL-1b induction
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ABSTRACT:
PROVIDER: PRJNA474112 | ENA |
REPOSITORIES: ENA
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Project description:Proper inflammatory responses are vital to restore tissue homeostasis against offending factors. However, it is largely under explored whether inflammatory responses are modulated by the Hippo effectors YAP/TAZ. To identify the transcription targets related to inflammatory reponses for YAP, we utilized human bronchioalveolar carcinoma cells H358 expressing YAP(5SA) or GFP (as a control) and treated with vehicle, TNFa or IL-1b, respectively. Our work disclosed the complex features of YAP/TAZ’s role in inflammatory responses.
2018-06-02 | GSE115207 | GEO
Project description:Treatment with IL-1b or TNFa enhance the proliferation of alveolar type 2 cells in organoid culture. Here, we examine the downstream mechanisms that enhance AEC2 proliferation after IL-1b and TNFa treatments, we performed RNA-seq analysis of AEC2s isolated from organoids 6 hrs after exposure to either cytokine. We identified 165 differentially expressed genes that were common in both IL-1b and TNFa treated AEC2s compared to saline treated controls.
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2019-10-01 | GSE132704 | GEO
Project description:Microarray analyses with cells/tissues overexpressing YAP have revealed many transcription targets of YAP (Dong et al, 2007; Zhao et al, 2008). However, as YAP induces transformation of non-cancerous cells, we thought many of known targets of YAP may be indirect consequence of transforming property of YAP. To identify the immediate transcription targets for YAP, we utilized immortalized mammary epithelial MCF-10A cells expressing a tamoxifen inducible, hyperactive (S127/381A) YAP mutant (MCF-10A ERT2-YAP 2SA). MCF-10A ERT2 and MCF-10A ERT2-YAP 2SA are generated. Each cell line was treated with 0.1% of ethanol (solvent) or 1uM of 4-hydroxytamoxifen for 2 or 6 hours. This makes 6 samples per set. The experiments were done in duplicate. The expression data from MCF-10A ERT2 and MCF-10A ERT2-YAP 2SA before tamoxifen treatment can serve as control.
2015-11-23 | E-GEOD-60579 | biostudies-arrayexpress
Project description:Timecourse of gene expression in HeLa cells (parental cells and clonal knockouts of MED12 and MED24) following induction by TNFa or IL-1b
| PRJNA548788 | ENA
Project description:Microarray analyses with cells/tissues overexpressing YAP have revealed many transcription targets of YAP (Dong et al, 2007; Zhao et al, 2008). However, as YAP induces transformation of non-cancerous cells, we thought many of known targets of YAP may be indirect consequence of transforming property of YAP. To identify the immediate transcription targets for YAP, we utilized immortalized mammary epithelial MCF-10A cells expressing a tamoxifen inducible, hyperactive (S127/381A) YAP mutant (MCF-10A ERT2-YAP 2SA).
2015-11-23 | GSE60579 | GEO
Project description:This study compares gene expression change upon expression of Yes-associated protein (YAP) wild-type or mutants in order to establish the importance of TEAD binding and WW domains in the gene-induction function of YAP. The results indicate that gene-induction is seriously comprised in YAP-S94A (TEAD binding domain mutant) expressing cells. And mutantion of WW domains (YAP-W1W2) also affect a fraction of YAP induced genes. Therefore both TEAD binding domain and WW domains are required for the full function of YAP in gene-induction. Experiment Overall Design: Four samples are included: 1. pQCXIH vector control; 2 YAP-WT expression; 3. YAP-S94A expression; 4. YAP-W1W2 expression. Gene expression profiles of YAP wild-type or mutants expressing cells were compared to that of vector control. Experiments were done in MCF10A mammary epithelial cells.
2010-01-19 | E-GEOD-13218 | biostudies-arrayexpress
Project description:siRNA-mediated inhibition compared to untreated cells and cells transfected with nonsense siRNA. Loss of contact inhibition and anchorage-independent growth are hallmarks of cancer cells. In this context, frequent inactivation of the Hippo pathway and subsequent nuclear enrichment of the transcriptional coactivator yes-associated protein (YAP) uncouple cell proliferation and anti-apoptosis from contact inhibition, associated with uncontrolled tumor growth and tumor cell dissemination. However, general molecular mechanisms of tumor-supporting YAP activity remain unclear. In this study, we show that overexpression and nuclear accumulation of YAP in hepatocytes and hepatocellular carcinoma (HCC) cells leads to an induction of the Notch pathways through transcriptional activation of the Notch ligand jagged-1 (Jag-1). This induction of Jag-1 strictly depends on binding of YAP to TEAD4 and does not rely on WNT/β-catenin pathway activity. Co-activation of YAP, TEAD4, Jag-1, and the Notch target gene Hes-1 was significantly higher in HCC from patients with poor prognosis. High-level expression and nuclear accumulation of YAP correlates with Jag-1/Notch activation not only in human HCC tissues, but also in colon and pancreatic cancer tissues. Thus, our data demonstrate that YAP-driven co-activation of the Jag-1/Notch pathway in part facilitates oncogenic properties of the oncogene YAP not only in HCC but also in different gastrointestinal malignancies. Expression profiling of untreated HCC cell lines (control 1), cells transfected with scrambled/nonsense siRNA (control 2), and after siRNA-mediated YAP inhibition.
2012-11-01 | E-GEOD-35004 | biostudies-arrayexpress
Project description:Constitutive androstane receptor (CAR) agonists, such as TCPOBOP, are known to cause robust hepatocyte proliferation and hepatomegaly in mice along with induction of drug metabolism genes, without any associated liver injury. Yes-associated protein (YAP) is a key transcription regulator that tightly controls organ size including that of liver. Ours and other previous studies suggested increased nuclear localization and activation of YAP after TCPOBOP treatment in mice and potential role of YAP in CAR-driven proliferative response. Here, we investigated a direct role of YAP in CAR-driven hepatomegaly and hepatocyte proliferation using hepatocyte-specific YAP-KO mice. AAV8-TBG-CRE vector was injected to YAP-floxed mice for achieving hepatocyte-specific YAP deletion followed by TCPOBOP treatment. YAP deletion did not alter protein expression of CAR or CAR-driven induction of drug metabolism genes (including Cyp2b10, Cyp2c55 and UGT1a1). However, YAP deletion substantially reduced TCPOBOP-induced hepatocyte proliferation. TCPOBOP-driven cell cycle activation was disrupted in YAP-KO mice due to delayed (and decreased) induction of cyclin D1 and higher expression of p21, resulting in decreased phosphorylation of retinoblastoma (Rb) protein. Further, induction of other cyclins, which are sequentially involved in progression through cell cycle (including cyclin E1, A2 and B1) and important mitotic regulators (such as aurora B kinase and polo-like kinase 1) was remarkably reduced in YAP-KO mice. Microarray analysis revealed that 26% of TCPOBOP‐responsive genes mainly related to proliferation, but not to drug metabolism, were altered by YAP deletion. YAP regulated these proliferation genes via alerting expression of cMyc and FOXM1, two critical transcriptional regulators of CAR-mediated hepatocyte proliferation. Conclusion: Our study revealed an important role of YAP signaling in CAR-driven hepatocyte proliferation; however, CAR-driven induction of drug metabolism genes was independent of YAP. We used microarrays to detail the global programme of gene expression in livers of hepatocyte-specific YAP KO mice following TCPOBOP treatment
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2023-05-19 | PXD032130 | Pride