Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expression data of cystic renal epithelial tissue from mice deficient for fumarate hydratase.

ABSTRACT: Fumarate hydratase (FH) mutations cause hereditary leiomyomatosis and renal cell cancer (HLRCC). We have conditionally inactivated the murine ortholog (Fh1) in renal tubular epithelial cells in order to generate an in vivo model of HLRCC. Fh1 knockout mice recapitulates important aspects of HLRCC including the development of renal cysts that overexpress hypoxia inducible factor alpha (Hifa) and Hif-target genes. We used microarrays to detail the global programme of gene expression underlying cyst development in Fh1 knockout mice and identified distinct classes of up-regulated genes during this process. Keywords: gene expression, comparison (wild-type n=3 vs knockout n=3)

ORGANISM(S): Mus musculus

PROVIDER: GSE10989 | GEO | 2010/12/22

SECONDARY ACCESSION(S): PRJNA107197

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression data of cystic renal epithelial tissue from mice deficient for fumarate hydratase.

Project description:Fumarate hydratase (FH) mutations cause hereditary leiomyomatosis and renal cell cancer (HLRCC). We have conditionally inactivated the murine ortholog (Fh1) in renal tubular epithelial cells in order to generate an in vivo model of HLRCC. Fh1 knockout mice recapitulates important aspects of HLRCC including the development of renal cysts that overexpress hypoxia inducible factor alpha (Hifa) and Hif-target genes. We used microarrays to detail the global programme of gene expression underlying cyst development in Fh1 knockout mice and identified distinct classes of up-regulated genes during this process. Keywords: gene expression, comparison (wild-type n=3 vs knockout n=3) Renal epithelial tissue was macro-dissected from Fh1 knockout mice and sex-matched litter mate control disease-free animals for RNA extraction and hybridization on Affymetrix microarrays.

2010-12-22 | E-GEOD-10989 | biostudies-arrayexpress

Fumarate induces vesicular release of mtDNA to drive innate immunity

Project description:Fumarate Hydratase (FH) is an enzyme of the Tricarboxilic Acid Cycle (TCA) that catalyzes the conversion of fumarate into malate. In the last decade, studies have revealed FH as a bona fide tumour suppressor whose mutations cause Hereditary leiomyomatosis and renal cell carcinoma (HLRCC). Loss of FH in the kidney elicits several oncogenic signalling cascades through the accumulation of the oncometabolite fumarate. Yet, whilst the long-term consequences of FH loss have been extensively described, the acute response to FH loss has not been investigated due, in part, to the lack of a suitable model. Here, we generated a new inducible mouse model to investigate the chronology of the murine homologue of FH, Fh1, loss in the adult kidney.

2023-02-17 | GSE183745 | GEO

Expression data from mouse kidney epithelial cells

Project description:Fumarate hydratase (FH) is the enzyme in the Krebs cycle, which transforms fumarate to malate. Loss of fumarate hyrdragase leads to hereditary leiomyomatosis and renal cell cancer (HLRCC). The biallelic inactivation has been highly accumulated in FH-deficient cells and is considered a major pro-oncogenic factor for HLRCC tumorigenesis. We used microarrays to understand the global readaptation of cell metabolism of gene expression underlying the truncated Krebs cycle by loss of function of fumarate hydratase. The fumarate hydratase wild type and knock out cells were generated for RNA extraction and hybridization on Affymetrix microarrays.

2014-11-19 | E-GEOD-63438 | biostudies-arrayexpress

Expression data from mouse kidney epithelial cells

2014-11-19 | GSE63438 | GEO

Gene expression profile of HLRCC associated renal cell cancer

Project description:Gene expression profiles of normal kidney (3 technical replicates) and a renal tumor (3 technical replicates) from a hereditary leiomyomatosis and renal cell cancer (HLRCC) patient carrying a germline mutation in the fumarate hydratase (FH) gene.

2010-12-31 | GSE20896 | GEO

Gene expression profile of HLRCC associated renal cell cancer

2010-12-31 | E-GEOD-20896 | biostudies-arrayexpress

HIRA loss transforms FH deficient cells [ChIP-Seq]

Project description:Fumarate Hydratase (FH) is a mitochondrial enzyme that catalyses the reversible hydration of fumarate to malate in the TCA cycle. Germline mutations of FH lead to HLRCC, a cancer syndrome characterised by a highly aggressive form of renal cancer(1). Although HLRCC tumours metastasise rapidly, FH-deficient mice develop premalignant cysts in the kidneys, rather than carcinomas(2). How Fh1-deficient cells overcome these tumour suppressive events during transformation is unknown. Here, we perform a genome-wide CRISPR/Cas9 screen to identify genes that, when ablated, enhance the proliferation of Fh1-deficient cells. We found that the depletion of the HIRA enhances proliferation and invasion of Fh1-deficient cells in vitro and in vivo. Mechanistically, Hira loss enables the activation of MYC and its target genes, increasing nucleotide metabolism specifically in Fh1-deficient cells, independent of its histone chaperone activity. These results are instrumental for understanding mechanisms of tumorigenesis in HLRCC and the development of targeted treatments for patients.

2022-10-29 | GSE203056 | GEO

An antioxidant response phenotype is shared between hereditary and sporadic type 2 papillary renal cell carcinoma

Project description:Fumarate hydratase (FH) mutation causes hereditary type 2 papillary renal cell carcinoma (HLRCC, Hereditary Leiomyomatosis and Renal Cell Cancer (MM ID # 605839)). The main effect of FH mutation is fumarate accumulation. The current paradigm posits that the main consequence of fumarate accumulation is HIF-a stabilization. Paradoxically, FH mutation differs from other HIF-a stabilizing mutations, such as VHL and SDH mutations, in its associated tumor types. We identified that fumarate can directly up-regulate antioxidant response element (ARE)-controlled genes. We demonstrated that AKR1B10 is an ARE-controlled gene and is up-regulated upon FH knockdown as well as in FH-null cell lines. AKR1B10 overexpression is also a prominent feature in both hereditary and sporadic PRCC2. This phenotype better explains the similarities between hereditary and sporadic PRCC2. Expression profiling renal normal and tumor tissue

2011-10-17 | E-GEOD-26574 | biostudies-arrayexpress

Mitochondrial DNA Alterations Underlie an Irreversible Shift to Aerobic Glycolysis in Fumarate Hydratase-deficient Renal Cancer

Project description:Understanding the mechanisms of the Warburg shift to aerobic glycolysis is central to defining the metabolic basis of cancer. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an aggressive cancer characterized by bi-allelic inactivation of the gene encoding the Krebs cycle enzyme fumarate hydratase, an early shift to aerobic glycolysis, and rapid metastasis. We observed of the mitochondrial in tumors from HLRCC patients. Biochemical and transcriptomics analyses revealed that respiratory chain dysfunction in the tumors was due to loss of expression of mitochondrial DNA (mtDNA)-encoded subunits of respiratory chain complexes, caused by a marked decrease in mtDNA content and increased mtDNA mutations. We demonstrated that accumulation of fumarate in HLRCC tumors inactivated the core factors responsible for replication and proofreading of mtDNA, leading to loss of expression of respiratory chain components, thereby promoting the shift to aerobic glycolysis and disease progression in this prototypic model of glucose-dependent human cancer.

2021-01-22 | GSE157256 | GEO

A chemoproteomic portrait of the oncometabolite fumarate

Project description:Hereditary cancer disorders often provide an important window into novel mechanisms supporting tumor growth and survival. Understanding these mechanisms and developing biomarkers to identify their presence thus represents a vital goal. Towards this goal, here we report a chemoproteomic map of the covalent targets of fumarate, an oncometabolite whose accumulation marks the genetic cancer predisposition syndrome hereditary leiomyomatosis and renal cell carcinoma (HLRCC). First, we validate the ability of known and novel chemoproteomic probes to report on concentration-dependent fumarate reactivity in vitro. Next, we apply these probes in concert with LC-MS/MS to identify cysteine residues sensitive to either fumarate treatment or fumarate hydratase (FH) mutation in untransformed and HLRCC cell models, respectively. Mining this data to understand the structural determinants of fumarate reactivity led to the discovery of an unexpected anti-correlation with nucleophilicity, indicating a novel influence of pH on fumarate-cysteine interactions. Finally, we show that many fumarate-sensitive and FH-regulated cysteines are found in functional protein domains, and perform functional studies of a fumarate-sensitive cysteine in SMARCC1 that lies at a key protein-protein interface in the SWI-SNF tumor suppressor complex. Our studies provide a powerful resource for understanding the influence of fumarate on reactive cysteine residues, and lay the foundation for future efforts to exploit this distinct aspect of oncometabolism for cancer diagnosis and therapy.

2018-11-27 | PXD009378 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data