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RNA-Seq analysis of HIF-2a-responsive genes in clear-cell renal cell carcinoma

ABSTRACT: RNA-Seq analysis of HIF-2a-responsive genes in clear-cell renal cell carcinoma

PROVIDER: PRJNA474756 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7267580_1.fastq.gz	Fastqsanger.gz
	SRR7267580_2.fastq.gz	Fastqsanger.gz
	SRR7267581_1.fastq.gz	Fastqsanger.gz
	SRR7267581_2.fastq.gz	Fastqsanger.gz
	SRR7267582_1.fastq.gz	Fastqsanger.gz

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RNA-Seq analysis of HIF-2a-responsive genes in clear-cell renal cell carcinoma

Project description:We performed RNA-Seq analysis of wildtype and three EPAS1-/- 786-O single cell clones generated by CRISPR/Cas9 to identify the HIF-2a-responsive genes in this cell line. Samples from wildtype 786-O cells treated with DMSO or HIF-2a antagonist compound C2 were also included in this analysis.

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HIF-1a and HIF-2a differently regulate tumour development, metabolism and inflammation of clear cell renal cell carcinoma in mice

Project description:Mutational inactivation of VHL is the earliest genetic event in the majority of clear cell renal cell carcinomas (ccRCC), leading to accumulation of the HIF-1alpha and HIF-2a transcription factors. While correlative studies of human ccRCC and functional studies using human ccRCC cell lines have implicated HIF-1a as an inhibitor and HIF-2a as a promoter of aggressive tumour behaviours, their roles in tumour onset have not been functionally addressed. Using an autochthonous ccRCC model, we show genetically that Hif1a is essential for tumour formation whereas Hif2a deletion has only minor effects on tumour initiation and growth. Both HIF-1a and HIF-2a are required for the clear cell phenotype. Transcriptomic and proteomic analyses revealed that HIF-1alpha regulates glycolysis while HIF-2a regulates genes associated with lipoprotein metabolism, ribosome biogenesis and E2F and MYC transcriptional activities. HIF-2a-deficient tumours were characterised by increased antigen presentation, interferon signalling and CD8+ T cell infiltration and activation. Single copy loss of HIF1A or high levels of HIF2A mRNA expression correlated with altered immune microenvironment in human ccRCC. These studies reveal an oncogenic role of HIF-1alpha in ccRCC initiation and suggest that alterations in the balance of HIF-1alpha and HIF-2a activities can affect different aspects of ccRCC biology and disease aggressiveness.

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Transcription profiling of human 786-O clear cell renal carcinoma cells reveals small molecule inhibitors of HIF-2a translation link its 5 UTR Iron-Responsive Element (IRE) to oxygen sensing

Project description:Cells transiently adapt to hypoxia by globally decreasing protein translation. However, specific proteins needed to respond to hypoxia evade this translational repression. The mechanisms of this phenomenon remain unclear. We screened for and identified small molecules that selectively decrease HIF-2a translation in an mTOR independent manner, by enhancing the binding of Iron Regulatory Protein 1 (IRP1) to a recently reported Iron-Responsive Element (IRE) within the 5â-untranslated region (UTR) of the HIF-2a message. Knocking down the expression of IRP1 by shRNA abolished the effect of the compounds. Hypoxia de-represses HIF-2a translation by disrupting the IRP1- HIF-2a IRE interaction. Thus, this chemical genetic analysis describes a molecular mechanism by which translation of the HIF-2a message is maintained during conditions of cellular hypoxia through inhibition of IRP-1 dependent repression. It also provides the chemical tools for studying this phenomenon. Experiment Overall Design: 3 replicate samples of 786-O human Clear Cell Renal Carcinoma cells untreated, mock treated with DMSO or treated with either of 4 HIF-2a inhibitor compounds identified by chemical genetic screening.

2009-01-14 | E-GEOD-13818 | biostudies-arrayexpress

HIF-1a and HIF-2a differently regulate tumour development, metabolism and inflammation of clear cell renal cell carcinoma in mice

Project description:HIF-1a and HIF-2a differently regulate tumour development, metabolism and inflammation of clear cell renal cell carcinoma in mice

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ChIP-chip from human liver cancer cells with HIF-2a

Project description:The transcription factor HIF-2a play an important role in the tumor progress, the aim is to explore the target genes of HIF-2a in liver cancer cell line. Chromatin immunoprecipitation (ChIP) of HIF-2a together with chromatin profiling by ChIP-on-chip analysis demonstrated that HIF-2a directly activates many target genes. Analyze the target genes in a liver cancer cell line MHCC97H

2012-04-11 | E-GEOD-37167 | biostudies-arrayexpress

HIF transcriptome in clear cell renal carcinoma cells

Project description:HIF transcriptome in clear cell renal carcinoma cells

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ChIP-chip from human liver cancer cells with HIF-2a

2012-04-12 | GSE37167 | GEO

PAR-CLIP of RBM4 and HIF-2a

Project description:To identify which mRNAs bind to RBM4/HIF-2a Two PAR-CLIPs were performed: One of an RBM4 immunoprecipitation, and the other of a HIF-2a immunoprecipitation and excising the associated RBM4 band.

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Project description:Mutational inactivation of VHL is the earliest genetic event in the majority of ccRCCs, leading to activation of the HIF-1α and HIF-2α transcription factors. While correlative studies of human ccRCCs and functional studies using human ccRCC cell lines have implicated HIF-1α as an inhibitor and HIF-2α as a promoter of aggressive tumour behaviours, their roles in tumour onset have not been functionally addressed. Using an autochthonous ccRCC model, we show genetically that Hif1a is necessary for tumour formation whereas Hif2a deletion has only minor effects on tumour initiation and growth. Both HIF-1α and HIF-2α are necessary for the clear cell phenotype. Transcriptomic and proteomic analyses revealed that HIF-1α regulates glycolysis while HIF-2α regulates genes associated with lipoprotein metabolism, ribosome biogenesis and E2F and MYC transcriptional activities. Deficiency of HIF-2α increased CD8+ T cell infiltration and activation. These studies reveal different functions of HIF-1α and HIF-2α in ccRCC. SIGNIFICANCE The roles of HIF-1α and HIF-2α in ccRCC pathogenesis remain unclear. Using a mouse genetic approach we show that HIF-1α but not HIF-2α is important for tumour formation, contrary to predictions from studies of human ccRCC. We show that HIF-1α and HIF-2α transcriptionally regulate different aspects of metabolism and identify HIF-2α as a suppressor of immune cell infiltration and activation.

2020-07-02 | PXD016630 | Pride

ChIP-seq analysis of HIF-1a and HIF-2a binding in hypoxic cancer cell lines

Project description:Pan-genomic analysis of hypoxic HIF-1a and HIF-2a binding by ChIP-seq in cancer cell lines

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