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

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

PROVIDER: PRJNA634318 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11825100_1.fastq.gz	Fastqsanger.gz
	SRR11825100_2.fastq.gz	Fastqsanger.gz
	SRR11825101_1.fastq.gz	Fastqsanger.gz
	SRR11825101_2.fastq.gz	Fastqsanger.gz
	SRR11825102_1.fastq.gz	Fastqsanger.gz

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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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Expression data from Mesenchymal progenitor cells knocked down for HIF-1a or HIF-2a expression

Project description:HIF-1a and HIF-2a are expressed at high levels in mesenchymal progenitors compared to more committed mesenchymal cells and hematopoietic cells. HIF-factors could therefore have a role in the regulation the biology of mesenchymal progenitors and their functions, like the non cell-autonomous maintenance of hematopoietic progenitors. We used microarrays to detail the global program of gene expression regulated by HIF-1a or HIF-2a in mesenchymal progenitors Mesenchymal progenitors were FACS-sorted and cultured in low oxygen concentration for few days. Once cells started to form CFU-F colonies, we transduced them with shRNAs targeting specifically HIF-1a or HIF-2a. Four days after transduction, cells were collected and RNA extracted for microarray analysis.

2014-03-25 | E-GEOD-56141 | biostudies-arrayexpress

Identification of hypoxia regulated HIF-1A and HIF-2A specific target genes in Glioblastoma

Project description:HIF-1A and HIF-2A regulate both overlapping and unique target genes in response to hypoxia. In this dataset, we identify specific HIF-1A and HIF-2A target genes in glioblastoma cells. 12 samples were analysed comprising 4 experimental conditions (normoxia scr, hypoxia scr, hypoxia siHIF1, hypoxia siHIF2) in triplicate. We made pairwise comparisons between the averages of each triplicate set to normoxia scr using the Partek suite.

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

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Transcription profiling of liver from mice with constitutively active Hypoxia Inducible Factor (HIF-1a and HIF-2a) or inactivated von Hippel-Lindau tumor suppressor gene product (pVHL)

Project description:The effects of constitutively active Hypoxia Inducible Factor (HIF) and inactivated von Hippel-Lindau tumor suppressor gene product (pVHL) were examined in a mouse model. Conditionally expressed, constitutively active HIF-1a and HIF-2a were compared with inactivated pVHL.

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

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

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HIF-1a and HIF-2a ChIP-seq and RNA-seq of hypoxic cancer cell lines

Project description:HIF-1a and HIF-2a ChIP-seq and RNA-seq of hypoxic cancer cell lines

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