MBOAT7 loss of function in clear cell Renal Carcinoma (ccRCC)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE131881 | GEO | 2020/02/26
REPOSITORIES: GEO
Similar Datasets
Project description:MBOAT7 loss of function in clear cell Renal Carcinoma (ccRCC)
| PRJNA545231 | ENA
Project description:Gene expression profiling was performed in ccRCC cells, which either express both HIF1alpha and HIF2alpha (either naturally or by virtue of induced expression of HIF1alpha) or express HIF2alpha alone (either naturally or by virtue of a HIF1alpha shRNA), to identify genes regulated by HIF1alpha in ccRCC cells. Three H2 cell lines 769P, A498, and SLR24 were stably infected with retrovirus encoding doxycycline-inducible Luciferase (control) or HIF1alpha, and two H1H2 cell lines Caki-2 and SLR25 were stably infected with retroviruses encoding scrambled (control) or HIF1alpha shRNA. Duplicated samples were used for each condition.
2011-12-02 | E-GEOD-27415 | biostudies-arrayexpress
Project description:To select signatures of ccRCC, 265 ccRCC samples were obtained from the Van Andel Research Institute. Gene expression profiles of 265 samples were determined using the HG-U133_Plus_2 platform.
2017-08-08 | GSE73731 | GEO
Project description:Objective: The rs641738C>T variant located near the membrane-bound O-acyltransferase domain containing 7 (MBOAT7) locus is associated with fibrosis in liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcohol-related liver disease, hepatitis B and C. We aim to understand the mechanism by which the rs641738C>T variant contributes to pathogenesis of NAFLD. Design: Mice with hepatocyte-specific deletion of MBOAT7 (Mboat7 Δhep) were generated and livers were characterised by histology, flow cytometry, qPCR, RNA sequencing and lipidomics. We analysed the association of rs641738C>T genotype with liver inflammation and fibrosis in 846 NAFLD patients and obtained genotype-specific liver lipidomes from 280 human biopsies. Results: Allelic imbalance analysis of heterozygous human liver samples pointed to lower expression of the MBOAT7 transcript on the rs641738C>T haplotype. Mboat7 Δhep mice showed spontaneous steatosis characterised by increased hepatic cholesterol ester content after 10 weeks. After 6 weeks on a high fat, methionine-low, choline-deficient diet, mice developed increased hepatic fibrosis as measured by picrosirius staining (p<0.05), hydroxyproline content (p<0.05) and transcriptomics, while the inflammatory cell populations and inflammatory mediators were minimally affected. In a human biopsied NAFLD cohort, MBOAT7 rs641738C>T was associated with fibrosis (p=0.004) independent of the presence of histological inflammation. Liver lipidomes of Mboat7 Δhep mice and human rs641738TT carriers with fibrosis showed increased total lysophosphatidylinositol (LPI) levels. The altered LPI and phosphatidylinositol subspecies in MBOAT7 Δhep livers and humans rs641738TT carriers were similar. Conclusion: Mboat7 deficiency in mice and human points to an inflammation-independent pathway of liver fibrosis that may be mediated by lipid signalling and a potentially targetable treatment option in NAFLD.
2020-06-30 | GSE139992 | GEO
Project description:A total of 3 metastatic and 3 non-metastatic ccRCC tissues were collected from patients. These tissues were flash frozen in liquid nitrogen immediately after surgery and subsequently stored at -80℃. All the resected nodules or metastatic masses were identified as renal tumor by pathologic examination. No patients received anticancer treatments before surgery in this study. We analyzed gene expression microarray data from our gene chip with 3 metastatic ccRCC tissues compared with 3 non-metastatic ccRCC tissues.
2017-08-17 | GSE88948 | GEO
Project description:Tumorigenic processes are understood to be driven by epi-/genetic and genomic alterations from single point mutations to chromosomal alterations such as insertions and deletions of nucleotides up to gains and losses of large chromosomal fragments including products of chromosomal rearrangements e.g. fusion genes and proteins. Overall comparisons of copy number alterations (CNAs) present in 48 clear cell renal cell carcinoma (ccRCC) genomes result in ratios of gene losses versus gene gains between 26 ccRCC Fuhrman malignancy grades G1 (ratio 1.25) and 20 G3 (ratio 0.58). Gene losses and gains of 15762 CNA genes are mapped to 795 chromosomal cytoband loci including 280 KEGG pathways. CNAs are classified according to their contribution to Fuhrman tumour gradings G1 and G3. Gene gains and losses turn out to be highly structured processes in ccRCC genomes enabling the subclassification and stratification of ccRCC tumours in a genome-wide manner. CNAs of ccRCC seem to start with common tumour related gene losses flanked by CNAs specifying Fuhrman grade G1 losses and CNA gains favouring grade G3 tumours. The appearance of recurrent CNA signatures implies the presence of causal mechanisms most likely implicated in the pathogenesis and disease-outcome of ccRCC tumours distinguishing lower from higher malignant tumours. Finally, the diagnostic quality of initial 201 genes (108 genes supporting G1 and 93 genes G3 phenotypes) are successfully validated on published Swiss data (GSE19949) leading to a restricted CNA gene set of 171 CNA genes of which 85 genes favour Fuhrman grade G1 and 86 genes Fuhrman grade G3. Regarding these gene sets overall survival decreases with the number of G3 related gene losses plus the total number of gene gains. CNA gene sets presented define an entry to a gene-directed and pathway-related functional understanding of ongoing copy number alterations within and between individual ccRCC tumours leading to CNA genes of prognostic and predictive value.
2017-06-09 | GSE95239 | GEO
Project description:Gene expression profiling was performed in ccRCC cells, which either express both HIF1alpha and HIF2alpha (either naturally or by virtue of induced expression of HIF1alpha) or express HIF2alpha alone (either naturally or by virtue of a HIF1alpha shRNA), to identify genes regulated by HIF1alpha in ccRCC cells.
2011-12-02 | GSE27415 | GEO
Project description:MethylCap-Seq experiments of 4 ccRCC cell lines (SKRC1, SKRC10, SKRC52, SKRC59) and one "normal" kidney cell line (HK2) were performed, and used, in combination with DAC/TSA re-expression data, to mine the ccRCC specific cancer methylome. Identified candidate DNA-methylation markers were evaluated by MSP in two independent series, yielding 4 validated markers (GREM1, NEURL, LAD1, NEFH) of which promoter methylation was highly predictive of survival.
2017-04-04 | GSE33954 | GEO
Project description:clariom D and miRNA v4.0 microarray analyses of 786-O, A498 and Caki-1 cells suntinib resistant cell lines and originator cell lines we used intergrated pathway network analysis to identify miRNA-target gene pairs involved in sunitinib resistance.
2021-09-02 | GSE183140 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly common and is a leading cause of end stage liver diseases such as cirrhosis and hepatocellular carcinoma. The rise in NAFLD closely parallels the global epidemic of obesity and type 2 diabetes mellitus (T2DM), and there is a clear interrelationship between abnormal lipid metabolism, insulin resistance, and NAFLD progression. Several genetic loci have been identified as contributors to NAFLD progression, all of which are consistently linked to abnormal lipid metabolic processes in the liver. The common loss-of-function variant rs641738 (C>T) near the gene encoding Membrane_x0002_Bound O-Acyltransferase 7 (MBOAT7) is associated with increased susceptibility to NAFLD as well as the entire spectrum of NAFLD progression. The MBOAT7 gene encodes a lipid metabolic enzyme that is capable of esterifying polyunsaturated fatty acyl-CoAs to LPI substrates to generate phosphatidylinositol (PI) lipids. We previously showed that antisense oligonucleotide (ASO)-mediated knockdown of Mboat7 in mice promoted high fat diet-induced hepatic steatosis, hyperinsulinemia, and systemic insulin resistance (Helsley et al., 2019). Thereafter, other groups showed that hepatocyte-specific genetic deletion of Mboat7 promoted striking fatty liver and NAFLD progression but does not alter insulin sensitivity, suggesting the potential for cell autonomous roles. Here, we show that MBOAT7 function in adipocytes contributes to diet- 3 induced metabolic disturbances including hyperinsulinemia and systemic insulin resistance. The expression of Mboat7 in white adipose tissue closely correlates with diet-induced obesity across a panel of ~100 inbred strains of mice fed a high fat/high sucrose diet. Moreover, adipocyte_x0002_specific genetic deletion of Mboat7 is sufficient to promote hyperinsulinemia, systemic insulin resistance, and mild fatty liver. Unlike in the liver, where Mboat7 plays a relatively minor role in maintaining arachidonic acid (AA)-containing PI pools, Mboat7 is the major source of AA_x0002_containing PI pools in adipose tissue. Our data demonstrate that MBOAT7 is a critical regulator of adipose tissue PI homeostasis, and adipocyte MBOAT7-driven PI biosynthesis is closely linked to hyperinsulinemia and insulin resistance in mice.
2023-04-04 | GSE203414 | GEO