Similar Datasets
Project description:Roles of RNF213 in temporal resonse to palmitate in HeLa cells
| PRJNA1367668 | ENA
Project description:Intrahepatic cholangiocarcinoma (ICC) is a lethal cancer arising from intrahepatic bile ducts in the liver. In the intraductal growth (IDG) type, also referred to as intraductal papillary neoplasm of the bile duct (IPNB), a rare subtype of ICC, cancer cells originating within the bile duct usually invade and infiltrate the nearby liver tissues, resulting in local invasion. IPNB can serve as a good disease model to study the mechanism of local invasion, which is the earliest step of metastasis. Here, we aimed to identify the genes associated with local invasion by comparing the somatic mutations of the matched IPNB tissues with and without local invasion from a set of 11 patients using the Ion AmpliSeq Comprehensive Cancer Panel. Somatic mutation profiling analysis identified RNF213 as a potential candidate gene associated with local invasion in ICC patients. We established stable RNF213-knockdown and shControl cholangiocarcinoma (CCA) cell lines (HuCCT1, YSCCC, and KKU-100). Next, the expression profiling of the RNF213-knockdown and shContol CCA cell lines was analyzed by RNA sequencing.
2024-07-24 | GSE235891 | GEO
Project description:Urticarial lesions are observed in both cutaneous and systemic disorders. Familial forms of urticarial syndromes are rare and can be encountered in systemic auto-inflammatory diseases. We investigated a large family with dominantly inherited chronic urticarial lesions associated with hypercytokinemia. We performed a genetic linkage analysis in 14 patients from a 5-generation family, as well as whole-exome sequencing, cytokine profiling and transcriptomic analyses on samples from two patients. The identified candidate protein was studied after in vitro expression of the corresponding normal and mutated recombinant proteins. An unsupervised proteomic approach was followed to unveil the associated protein network. The disease phenotype of the most affected family members is characterized by chronic urticarial flares associated with extremely high plasma levels of pro- (IL-1b, IL-6, TNF-a) and anti-inflammatory (IL-10, IL1-RA) cytokines, with no secondary organ dysfunction, no susceptibility to infections, no fever and normal C-reactive protein levels. Monocyte transcriptomic analyses identified an immunotolerant profile in the most affected patient. Affected family members carried a loss-of-function mutation in RNF213 that encodes mysterin, a protein of poorly known physiological role. We identified the deubiquitinase CYLD, a major regulator of inflammation, as an RNF213 partner and showed that CYLD expression is inhibited by wild-type but not mutant RNF213. We identified a new entity characterized by chronic urticarial lesions associated with a clinically-blunted hypercytokinemia. This disease, due to a loss of function of RNF213, reveals mysterin’s key role in the complex molecular network of innate immunity.
2022-07-01 | GSE168721 | GEO
Project description:To study the role of RNF213, we generated RNF213-deficient human cerebral microvascular endothelial cells by the CRISPR-Cas9 double nickase method and showed that RNF213 may be an important regulator of the blood-brain barrier permeability and homeostasis
2021-09-08 | GSE183603 | GEO
Project description:RNA sequencing technology was applied to determine the transcriptional changes due to palmitate treatment, RNF213 knockdown, and GPAT4 knockdown.
2019-01-17 | GSE125178 | GEO
Project description:RNF213 is a large, poorly characterized interferon-induced protein. Mutations in RNF213 are associated with predisposition for Moyamoya disease (MMD), a rare cerebrovascular disorder. Recently, RNF213 was found to have broad antimicrobial activity in vitro and in vivo, yet the molecular mechanisms behind this function remain unclear. Using mass spectrometry-based proteomics and validation by real-time PCR we here report that knockdown of RNF213 leads to transcriptional upregulation of MVP and downregulation of CYR61, in line with reported pro- and anti-bacterial activities of these proteins. Knockdown of RNF213 also results in downregulation of DDAH1, which we discover to exert anti-microbial activity against Listeria monocytogenes infection. DDAH1 regulates production nitric oxide (NO), a molecule with both vascular and antimicrobial effects. We show that NO production is reduced in macrophages from RNF213 KO mice, suggesting that RNF213 controls Listeria infection through regulation of DDAH1 transcription and production of NO. Our findings propose a potential mechanism for the antilisterial activity of RNF213 and highlight NO as a potential link between RNF213-mediated immune responses and the development of MMD.
2022-02-17 | PXD027130 | Pride
Project description:RNF213-associated urticarial lesions with hypercytokinemia
| PRJNA713772 | ENA
Project description:Obesity-induced insulin resistance of the liver is characterised by increased gluconeogenesis, which contributes to elevated blood glucose levels in individuals with type 2 diabetes. Research into how fatty acids induce insulin resistance has commonly focused on the induction of insulin resistance. We hypothesise that by shifting focus to the reversal of an insulin resistant phenotype, novel insights can be made into the mechanisms by which insulin resistance can be overcome. Using global gene and lipid expression profiling, we aimed to identify biological pathways altered in parallel with restoration of palmitate-induced deregulation of glucose production using metformin and sodium salicylate. FAO hepatoma cells were treated with palmitate (0.075mM, 48h) with or without metformin (0.25mM) and sodium salicylate (2mM) in the final 24h of palmitate treatment, and effects on glucose production were determined. Microarray followed by gene set enrichment analysis was performed to investigate pathway regulation. A lipidomic analysis (HPLC-MS/MS) and measurement of secreted bile acids and cholesterol were performed. Reversal of palmitate-induced impairment of glucose production by metformin and sodium salicylate was characterised by down-regulated expression of metabolic pathways regulating acetyl-CoA to cholesterol and bile acid biosynthesis. Total levels of intracellular and secreted cholesterol and bile acids were not different between impaired and restored glucose production. Total intracellular levels of diacylgycerol, triacylglycerol and cholesterol esters increased with palmitate (impaired glucose production), however, these were not further altered with metformin and sodium salicylate (restored glucose production). Six individual lipid species containing 18:0 and 18:1 side-chains were reduced by metformin and sodium salicylate. Widespread lipid metabolism changes induced by the reversal of palmitate-induced deregulation of glucose production with metformin and sodium salicylate were identified. While cholesterol and bile acid levels remained unchanged, the flux through these pathways may in part explain these findings. The identification of lipid species containing 18:0 and 18:1 side chains being regulated alongside changes to glucose production may indicate potential mediators of glucose production and insulin resistance. Three-condition experiment, Vehicle, Palmitate (PA) and Palmitate (PA) + Metformin (Met) + Sodium Sailcylate (NaS) with biological replicates: 8 Vehicle, 20 PA and 20 PA+Met+NaS , independently grown and harvested. One replicate per array.
2013-11-08 | E-GEOD-52204 | biostudies-arrayexpress
Project description:We performed transcriptome analysis of HCAECs upon treatment with siRNF213 or with a control siRNA. Overall, a total of 217 genes were up-regulated (> 2.0-fold change in expression), while 499 genes were down-regulated (< 0.5-fold change in expression), in the siRNF213-treated cells when compared to the control. Expression of four genes (RNF213, CyclinA, B and E) from this signature was quantified in the same RNA samples by real-time PCR. Gene expression in HCAECs upon treatment with siRNF213 or with a control siRNA. Two independent experiments were performed at each condition.
2015-08-10 | E-GEOD-62348 | biostudies-arrayexpress
Project description:We performed transcriptome analysis of HCAECs upon treatment with siRNF213 or with a control siRNA. Overall, a total of 217 genes were up-regulated (> 2.0-fold change in expression), while 499 genes were down-regulated (< 0.5-fold change in expression), in the siRNF213-treated cells when compared to the control. Expression of four genes (RNF213, CyclinA, B and E) from this signature was quantified in the same RNA samples by real-time PCR.
2015-08-10 | GSE62348 | GEO