Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1146764 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30200461_1.fastq.gz | Fastqsanger.gz | |||
| SRR30200461_2.fastq.gz | Fastqsanger.gz | |||
| SRR30200462_1.fastq.gz | Fastqsanger.gz | |||
| SRR30200462_2.fastq.gz | Fastqsanger.gz | |||
| SRR30200463_1.fastq.gz | Fastqsanger.gz |
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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).
2010-03-23 | E-GEOD-15205 | biostudies-arrayexpress
Project description:Background: Cutaneous malignant melanoma (CMM) is one of the most highly fatal cancers; its pathogenesis requires study. We recognize that abnormalities in lipid metabolism may be associated with the risk of CMM development; nevertheless, the role of lipid metabolism in the proliferation, invasion, and metastasis of CMM remains unclear. Methods: Lipid metabolism-related genes were identified in MsigDB. A lipid metabolism-related predictive model was constructed in TCGA-SKCM using univariate Cox regression analysis, consensus cluster analysis, WGCNA analysis, LASSO regression analysis, and outcomes-related genes were identified. Immunohistochemistry, qPCR, and western blotting were used to identify essential genes, construct stable lentivirus strains, and study the biological role of PLEKHA5 in CMM cells. Transcriptomic and proteomic sequencing, protein-protein molecular docking, CO-IP, and GST pull-down were performed on the cells with knockout essential genes to explore this gene’s upstream and downstream regulatory mechanisms. After analyzing the results of lipid metabolomics sequencing, the effects of the essential lipids related to CMM cells after the gene knockdown were studied. Results: A predictive model was established, Risk Score = -0.009 * UBE2L6 + 0.033 * PLEKHA5 + 0.024 * LHB + 0.036 * CARM1 + 0.016 * PRXL2B + 0.131 * PLA2G4D. PLEKHA5 was identified as an essential gene, and PLEKHA5 was positively correlated with poor outcomes in CMM patients. PLEKHA5 is more highly expressed than melanocytes in CMM, which promotes the proliferation, invasion, and metastasis of CMM. FCRLA is the downstream gene of PLEKHA5, upregulated in CMM, and the primary enrichment pathway is the TNFα-NFκB signaling pathway. TNFα is also an essential cytokine that promotes CMM proliferation and metastasis. Hex1Cer(d18:1/26:2) and Cer(d18:2/26:2) in the downstream were significantly decreased, while ChE(0:0), ChE(18:0) and TG(18:0/16:0/19:0) in the downstream were significantly increased. The cholesterol ester inhibitor avasimibe inhibits CMM proliferation, metastasis, and invasion. Conclusion: The predictive model of CMM related to lipid metabolism established in this study has good predictive ability. PLEKHA5 is an essential biomarker related to lipid metabolism in CMM. TNFα-PLEKHA5-FCRLA is a signal axis that promotes proliferation, metastasis, and invasion of CMM. Its downstream product, the cholesterol ester inhibitor avasimibe, may treat CMM.
2024-08-12 | PXD054835 |
Project description:Pathenogenesis of atherosclerosis results from the interactions between disrupted lipid homeostasis and immune response, but the molecular bridges between the major players are still a matter of controversy. We performed a systemic study of the imflammatory cytokine tumor necrosis factor alpha (TNF alpha), a well established anorexia agent, in the livers of the mice exposed to 20h-cytokine/starvation. We show that treatment with TNF-alpha reverses adaptations to fasting. Moreover, it up-regulates cholesterol biosynthesis and down-regulates bile acids synthesis, which leads to disrupted cholesterol homeostasis and pro-atherogenic changes. Interestingly, we found that TNF alpha also interferes with gene regulation of the xenobiotic metabolism. Keywords: treatment and diet effects Mice have been either saline treated (nontreated group), saline treated and fasted for 20h (fasted group), and TNF-alpha treated (30 mikrograms per animal) and fasted for 20h (TNF-alpha group). 3 biological replicas from fasted and TNF-alpha groups were co-hybridized with pool of nontreated group. No dye-swaps were performed.
2010-05-25 | E-GEOD-6423 | biostudies-arrayexpress
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)-α, 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-α 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-α-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-α-induced-EMT, and the interference of the complex formation can be a new strategy for the fibrotic disorders.
2010-03-11 | GSE15205 | GEO
Project description:Cancer stem cells (CSCs) play a key role in tumour growth and metastasis. Although an expansion of CSC population was previously described in advanced cutaneous squamous cell carcinoma (SCC), it remains unknown whether CSC regulatory mechanisms also change through tumour progression to promote malignancy. Here, we generate mouse models of skin SCCs to study alterations in CSC regulation over progression. We found that features of CSCs change at late stage of progression, correlating with a switch from epithelial to mesenchymal tumour shape. beta-catenin and EGFR signalling are down-regulated, whereas autocrine FGFR1 and PDGFR alpha pathways are up-regulated in CSCs of advanced tumours. Inhibition of FGFR and PDGFR signalling repress malignant SCCs growth and metastasis, respectively. An enhanced epithelial-to-mesenchymal transition (EMT) program and over-expression of PDGFR alpha and FGFR1 are observed in malignant human skin SCCs, suggesting that these pathways are also induced over human SCC progression. Therefore, uncover signalling pathways controlling CSCs at specific stage of progression may improve the selection of more accurate targeted therapeutic strategies according to tumour stage, blocking SCC relapse and metastasis. Mouse models of skin SCCs progression were first generated. For that, individual samples of spontaneous or DMBA-TPA induced skin SCCs generated in K14-HPV16 mice were orthotopically engrafted in immunodeficient mice and then serially transplanted, generating lineages in which the progression from WD-SCCs to PD-SCCs was observed. Then, tumour cells expressing CD34 and alpha 6-integrin, previously identified as cutaneous cancer stem cells, were isolated by flow cytometry-sorter from WD-SCCs and PD-SCCs of different tumour lineages. RNA extraction and hybridization on Affymetrix microarrays was carried out to compare whole gene profiling of these populations of CSCs.
2016-01-08 | E-GEOD-59439 | biostudies-arrayexpress
Project description:Pathenogenesis of atherosclerosis results from the interactions between disrupted lipid homeostasis and immune response, but the molecular bridges between the major players are still a matter of controversy. We performed a systemic study of the imflammatory cytokine tumor necrosis factor alpha (TNF alpha), a well established anorexia agent, in the livers of the mice exposed to 20h-cytokine/starvation. We show that treatment with TNF-alpha reverses adaptations to fasting. Moreover, it up-regulates cholesterol biosynthesis and down-regulates bile acids synthesis, which leads to disrupted cholesterol homeostasis and pro-atherogenic changes. Interestingly, we found that TNF alpha also interferes with gene regulation of the xenobiotic metabolism. Keywords: treatment and diet effects
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