Gene expression profiles after knockdown of Nardilysin in TMK-1 gastric cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE29144 | GEO | 2011/05/16
SECONDARY ACCESSION(S): PRJNA140349
REPOSITORIES: GEO
Similar Datasets
Project description:Nardilysin (NRDc), a metalloendopeptidase of the M16 family, has been reported to promote the ectodomain shedding and resulting activation of various growth factors and cytokines, but its role in cancer biology have not been elucidated. Microarray experiments were performed to analyze the chnages of gene expression profiles after knockdown of NRDc by microRNA (miR)-based RNA interference (RNAi). RNAi experiments were perfomed using BLOCK-iT Pol II miR RNAi Expression Vector Kit with EmGFP (Invitrogen). TMK-1 cells stably expressing conrol or NRDc-targeting miR vector were established.
2011-05-16 | E-GEOD-29144 | biostudies-arrayexpress
Project description:Myocardial infarction (MI) contributes to cardiac mortality and morbidity. After myocardial infarction the innate immune response is pivotal in clearing of tissue debris as well as scar formation, but exaggerated cytokine and chemokine secretion with subsequent leukocyte infiltration also leads to further tissue damage. Post-translational regulation of cytokine / chemokine signaling occurs via ectodomain shedding through a disintegrin and metalloproteases (ADAMs). Here, we address the value of targeting a previously unknown ADAM10 / CX3CL1 axis in the regulation of neutrophil recruitment early after MI. We show that myocardial ADAM10 is distinctly upregulated in biopsies from patients with ischemia-driven cardiomyopathy and correlates with heart failure progression. Intriguingly, upon MI in mice, pharmacological treatment with the ADAM10 inhibitionor GI254023X as well as genetic cardiomycyte-specific ADAM10 deletion improves survival with markedly enhanced heart function and reduced scar size. Mechanistically, this is driven by abolished ADAM10-mediated CX3CL1 ectodomain shedding followed by diminished IL-1β-dependent inflammation, reduced neutrophil bone marrow egress as well as myocardial tissue infiltration. Genetic cardiomycyte-specific ADAM10 deletion confirmes the small-molecule data and leads to improved cardiac function and reduction in inflammatory markers after ischemic myocardial injury. Thus, our data shows a conceptual insight into how acute MI induces chemotactic signaling via ectodomain shedding in cardiomyocytes.
2022-11-10 | GSE217268 | GEO
Project description:CD8+ T cell immune responses are regulated by multi-layer networks, while the post-translational regulations remain largely unknown. Transmembrane ectodomain shedding is an important post-translational process regulating receptor expression and signal transduction by proteolytic cleavage of membrane proteins. Here, by targeting sheddase A Disintegrin and Metalloprotease (ADAM)17, we defined a post-translational regulatory mechanism mediated by ectodomain shedding in CD8+ T cells. Transcriptomic and proteomic analysis revealed the involvement of post-transcriptional/translational regulations in CD8+ T cells. T cell-specific deletion of ADAM17 led to a dramatic increase of effector CD8+ T cell differentiation and enhanced cytolytic effects to eliminate pathogens and tumors. Mechanistically, ADAM17 regulated CD8+ T cells by cleavage of membrane CD122. ADAM17 deficient CD8+ T cells had elevated CD122 expression and response to cytokines IL-2 and IL-15. Intriguingly, inhibition of ADAM17 in CD8+ T cells improved the efficacy of chimeric antigen receptor (CAR) T cells in solid tumor. Our findings reveal a critical post-translational regulation in CD8+ T cells, providing a potential therapeutic strategy of targeting ADAM17 for effective anti-tumor immunity. We then performed gene expression profiling analysis using data obtained from RNA-seq of 10 samples from two groups.
2024-07-20 | GSE236582 | GEO
Project description:We used RNA microarray to investigate the expression of full-time and part-time sheddases and their substrates in basal cell carcinoma when compared to squamous cell carcinoma and normal skin. We aimed to identify the involvement of these sheddases in CD200 ectodomain shedding. RNA was extracted from whole primary tissues and sent for sequencing. raw sequencing data was then processed in R using 'lumi' and 'limma' packages.
2022-08-25 | E-MTAB-12034 | biostudies-arrayexpress
Project description:Ectodomain shedding, which is the proteolytic release of transmembrane proteins from the cell surface, is crucial for cell-to-cell communication and other biological processes. The metalloproteinase ADAM17 mediates ectodomain shedding of over 50 transmembrane proteins ranging from cytokines and growth factors, such as TNF and EGFR ligands, to signaling receptors and adhesion molecules. Yet, the ADAM17 sheddome is only partly defined and biological functions of the protease have not been fully characterized. Some ADAM17 substrates (e.g. HB-EGF) are known to bind to heparan sulfate proteoglycans (HSPG), and we hypothesised that such substrates would be under-represented in traditional secretome analyses, due to their binding to cell surface or pericellular HSPGs. Thus, to identify novel HSPG-binding ADAM17 substrates, we developed a proteomic workflow that involves addition of heparin to solubilize HSPG-binding proteins from the cell layer, thereby allowing their mass spectrometry detection by heparin-secretome (HEP-SEC) analysis. Applying this methodology to murine embryonic fibroblasts stimulated with an ADAM17 activator enabled us to identify 47 transmembrane proteins that were shed in response to ADAM17 activation. This included known HSPG-binding ADAM17 substrates (i.e. HB-EGF, CX3CL1) and 14 novel HSPG-binding putative ADAM17 substrates.
2024-10-15 | PXD055223 | Pride
Project description:The goal of this data set is to identify transcriptional changes in activin-2 RNAi animals vs control animals. We did bulk RNA sequencing of a wound induced time course to try to identify changes in the context of activin-2 RNAi, and targets of activin-2. These changes may help explain some of the phenotypic chnages seen in activin-2 RNAi animals.
2020-05-15 | GSE148376 | GEO
Project description:Disintegrin and metalloproteinases ADAM10 and ADAM17 can release the extracellular region of a variety of membrane-bound proteins including cytokines, adhesion molecules, growth factors and receptors, important for many biological functions (ectodomain shedding).. So far, substrate identification for ADAM10 and ADAM17 focused exclusively on their membrane-anchored forms and their function as sheddases. With ADAM8 we now describe the first protease capable of releasing the ADAM17 ectodomain. Based on these findings, we investigated whether the soluble ectodomains of ADAM10 and ADAM17 still exhibit shedding activity and to determine their soluble protein substrate pool . To address this, a mass spectrometry-based N-terminomics approach (TAILS) was used to identify potential targets of soluble ADAM10 and ADAM17 (sADAM10/17) within the secretome of the murine cardiomyocyte cell line HL-1. We identified almost 140 protein cleavage events in total and 45 common substrates for both sADAM10 and sADAM17. Further in-vitro studies confirmed fibronectin, cystatin C, sN-cadherin, PCPE-1 as well as sAPP as direct substrates of soluble ADAM10 and/or ADAM17. Overall, we present the first degradome study for sADAM10 and sADAM17, thereby introducing a new regulation mode of the proteolytic activity of these essential proteases within the protease web.
2019-06-24 | PXD013718 | Pride
Project description:Betaglycan/type III TGF-β receptor (TGFBR3) is an established co-receptor for the TGF-β superfamily with direct binding demonstrated for TGF-β 1-3 and inhibin A. Betaglycan can be membrane-bound or have its ectodomain cleaved/ shed to produce soluble-betaglycan that has been demonstrated to sequester ligands. Extracellular domain of betaglycan is modified with glycosaminoglycan chains at Ser residues S534 and S545, to which heparan sulfate and chondroitin sulfate chains are covalently attached. To delineate the contribution of the heparan and chondroitin sulfate modifications on betaglycan on its shedding and thereby on TGF-β signaling in ovarian cancer biology, we used mutants of betaglycan with alterations to the different glycosaminoglycan modifications. We made the unexpected discovery that the heparan sulfate modifications are essential for maximum ectodomain shedding of betaglycan, which is further essential for the ability of betaglycan to suppress TGF-β signaling and the tumor cells responses to exogenous TGF-β ligand. Using unbiased transcriptomics, we identified TIMP3 as a key regulator of betaglycan shedding and thereby TGF-β signaling. Taken together, these studies are the first to demonstrate a critical link between the well-known modifications on betaglycan and TGF-β signaling responses.
2024-02-21 | GSE237403 | GEO
Project description:In mammals, RNA interference (RNAi) is mostly studied as a cytoplasmic event, however, numerous reports convincingly show nuclear localization of the AGO proteins. Nevertheless, the mechanism of nuclear entry remains to be fully elucidated, and the extent of nuclear RNAi further explored. We found that reduced Lamin A levels significantly induced nuclear influx of AGO2 in SHSY5Y neuroblastoma and A375 melanoma cancer cell lines, which normally have no nuclear AGO2. The translocation of AGO2 was accompanied by aggravated cell proliferation and we further found that the loss of Lamin A leads to EGFR and Src kinase activation, which regulates the turnover and stability of cytoplasmic AGO2. Furthermore, Lamin A KO significantly reduced the activity of nuclear RNAi. This was evident by AGO fPAR-CLIP in WT and Lamin A KO cells, where we observed ca 60% less efficiency of RNAi. Mass spectrometry of AGO interactome, from the nuclear fraction, indicated that AGO2 is in complex with FAM120A, a known interactor of AGO2 that reduces the activity of RNAi by competing with AGO2 transcript binding. Therefore, loss of Lamin A starts a signaling cascade that mediates nuclear AGO2 translocation to rapidly inhibit RNAi in order to facilitate cancer proliferation
2024-10-17 | PXD042899 | Pride
Project description:Renal cell carcinoma (RCC), the third most prevalent urological cancer, claims more than 100,000 lives/year worldwide. The clear cell (ccRCC) is the most common and aggressive subtype of renal cancer. Commonly asymptomatic, more than 30% of ccRCCs are diagnosed when they are already metastatic resulting in a 95% mortality rate and one-third of organ-confined cancers treated by nephrectomy develop metastasis during the follow-up. Diagnosis and monitoring requires expensive and frequent imaging examinations; thereby, finding of diagnostic and prognostic biomarkers to screen, diagnose and monitor renal cancers are clearly needed. Hepatitis A virus receptor/kidney injury molecule 1 (HAVCR1/KIM-1) gene has been claimed to be a susceptibility gene for ccRCC and HAVCR1/KIM-1 ectodomain shedding a predictive biomarker of tumor progression.
2020-09-27 | E-MTAB-2071 | biostudies-arrayexpress