Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expression profile after stable HIF-1a inhibition in gastric cancer cells under normoxic conditions

ABSTRACT: Based on the results of numerous clinical and preclinical analyses, the transcription factor HIF-1a has been identified as an important tumor-promoting factor and is considered to be an attractive target for cancer therapy. To further deconstruct the molecular nature of HIF-1a’s role in tumorigenesis, we have applied lentiviral shRNA transduction to establish HIF-1a-deficient gastric cancer cells. Interestingly, functional analyses failed to show a significant growth defect of HIF-1a-deficient gastric cancer cells in vitro and in vivo. These observations led us to propose that stable inactivation of HIF-1a resulted in efficient compensation enabling cell growth and, ultimately, tumor progression in a HIF-1a-independent manner. To better understand the mechanisms that control this compensation, we performed transcriptomics of control (“scrambled” (SCR)) and HIF-1a-deficient (HIF) gastric cancer cells. Analysis of hypoxia-inducible factor-1alpha (HIF-1a)-deficient gastric cancer cells under normoxia. The transcription factor HIF-1a is a key regulator of oxygen homeostasis and has been identified as an important tumor-promoting factor. Results provide insight into the role of HIF-1a in gastric carcinogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE57200 | GEO | 2017/02/11

SECONDARY ACCESSION(S): PRJNA245899

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Citrullination modulation maintains HIF-1A stabilization to drive tumor progression

Project description:HIF-1 (Hypoxia-inducible factor 1) is the master regulator responding to hypoxic conditions. Here, we found that HIF-1A is citrullinated by peptidyl arginine deiminase 4 (PADI4) at arginine 698, promoting HIF-1A stabilization and thus HIF-1-driven tumor growth. The knockdown of PADI4 could dramatically decrease HIF-1 protein expression without affecting the mRNA level, and this could be rescued by the proteasome inhibitor MG132 treatment under hypoxia. And PADI4-HIF-1A interaction is critical for HIF-1A stability and tumor progression, depending on the enzymatic activity of PADI4 and the pocket structure of PADI4. DHE, an FDA-approved agent for the treatment of migraine, was found serve as a potential antitumor agent throgh disrupting PADI4-HIF-1A interaction and suppressing HIF-1A stability. Taken together, we found the anti-tumor effect of DHE due to its effect on blocking PADI4-HIF-1A interaction and downregulating HIF-1A pathway in cancer cells. To figure out the influence of DHE on liver cancer cell under hypoxia, we treated Hep3B cell lines with two does DHE in 6 hours under Hypoxia and extracted mRNA for furthur RNA seq.

2024-05-28 | GSE233772 | GEO

Global genomic profiling of HIF-1a-regulated genes in bone marrow B cells under hypoxia or normoxia

Project description:HIF-1a works as a stress-induced transcription factor to induce target genes mediating cell proliferation, meabolism and inflammation. To gain new insights into HIF-1a biology, we used high-throughput sequencing to analyze global HIF-1a transcriptional networks in WT or HIF-1a deficient bone marrow B cells under hypoxia or normoxia.

2022-02-24 | GSE163848 | GEO

Single-cell sequecing of LCMV-specific WT and HIF-1a-deficient CD8 T cells isolated from LCMV-Clone13 infected host mice

Project description:To determine the role of hypoxia-inducible factor 1 alpha (HIF-1a) in exhausted T cells, we crossed Hif1a-fl/fl Cd4-Cre mice to tdTomato+ P14 animals and adoptively co-transferred equal numbers of WT and HIF-1a-deficient P14 CD8+ T cells into chronically infected WT host mice. 21 days post infection, we retrieved GFP+ (WT) and tdTomato+ (HIF-1a-deficient) donor P14 T cells by FACS sorting and subjected CITE-seq antibody-barcoded WT and HIF-1a-deficient CD8+ P14 T cells to multiplexed scRNA sequencing analysis.

2023-09-22 | GSE213847 | GEO

Gene Expression profiles of colon from Hif-1α+/+, Hif-1αLSL/LSL

Project description:To investigate the detailed molecular mechanisms for the regulatory role of HIF-1α in colon, microarray gene expression analysis was performed on colon RNA isolated from 6- to 8-week-old Hif-1α+/+, Hif-1αLSL/LSL mice. Background & Aims: The progression and growth of solid tumors leads to a state where tumors outgrow their capacity for efficient oxygenation and nutrient uptake and an increase in tumor hypoxia. Tumor hypoxic response is mediated by hypoxia-inducible factor (HIF)-1a and HIF-2a. These transcription factors regulate a battery of genes that are critical for tumor oxygenation, tumor metabolism, and cell proliferation and survival. Therefore, inhibitors of HIF have been sought for as anti-neoplastic agents in several different kinds of cancers. Interestingly, in ischemic and inflammatory diseases of the intestine, activation of HIF-1a is beneficial, and can reduce intestinal inflammation. The efficacy of pharmacological agents that chronically activate HIF-1a are decreased due to the tumorigenic potential of HIF. However, recent advance in understanding HIF signaling have identified mechanisms, which could allow for isoform specific activators. Activation of HIF-2a increases colon carcinogenesis and progression in mouse models. However, the role of chronic HIF-1a activation is unclear in the progression in colon cancer. The present data demonstrates that activation of HIF-1a in epithelial cells does not increase colon carcinogens or progression in two mouse models of colon cancer, and provides the proof of principle that HIF-1a activation maybe safe as therapies for inflammatory bowel disease. Global gene expression profiling in colon RNAs isolated from 6- to 8-week-old Hif-1α+/+ (n=5, Shah 019) and Hif-1αLSL/LSL (n=5, Shah 020).

2014-05-14 | E-GEOD-55915 | biostudies-arrayexpress

Siah2-dependent concerted activity of HIF and FoxA2 regulates formation of neuroendocrine prostate tumors

Project description:Neuroendocrine (NE) carcinoma and NE differentiation (NED) of human prostate tumor are hallmarks of aggressive human prostate cancer. Here we reveal that HIF-1a cooperation with FoxA2, a transcription factor expressed in NE tissue, is required for determining NE phenotype. Reduced HIF-1a expression, as seen in the E3 ubiquitin ligase Siah2 mutant mice, converted NE tumors to atypical hyperplasia when crossed with the TRAMPTg mice. Significantly, HIF-1a cooperation with FoxA2 enables the trans-activation of select HRE-regulated genes such as Hes6, Plod2 and Jmjd1a, whose expression is notably higher in metastatic prostate adenocarcinomas. Our findings disclose the requirement for spatial and timely regulation of FoxA2 and HIF-1a for NE/NED in prostate tumors. 12 prostate tumor samples were analyzed during normoxia and hypoxia, with different FOX/HIF genotypes. The pivotal samples are represented as duplicates.

2010-07-13 | E-GEOD-18478 | biostudies-arrayexpress

Gene Expression profiles of colon from Hif-1α+/+, Hif-1αLSL/LSL

2014-05-14 | GSE55915 | GEO

The role of HIF in FH-associated renal neoplasia

Project description:Fumarate hydratase (FH) mutations predispose to renal cysts cancer. These cancers overexpress hypoxia-inducible factor-alpha (Hif-1a). We have generated a conditional Fh1 (mouse FH) knockout mice that develop renal cysts and overexpress Hif-1a. In order to identify the contribution of Hif-1a to cyst formation we have intercrossed our mice with conditional HIf-1a KO mice.

2011-10-24 | GSE29988 | GEO

Characterization of in vitro cultured alveolar macrophages (AM) transcriptomes [bulk RNA-seq]

Project description:To identify molecular characteristics of WT AM without Wnt3a, and WT, b-catenin-deficient or HIF-1a-deficient AM with Wnt3a stimulation in vitro, we isolated RNA from AMs with various treatments and examined by bulk RNA-seq. We found a large number of gene profiles were altered following Wnt3a treatment in WT AMs, while b-catenin and HIF-1a deficiency largely abolished the effects of Wnt3a treatment on AM transcription, suggesting that b-catenin and HIF-1a mediates most downstream effects of Wnt3a in AMs. Indeed,HIF-1a-deficient AMs essentially phenocopied those of b-catenin-deficient AMs, with more than 80% of differentially expressed genes in HIF-1a-deficient AMs overlapping with b-catenin-deficient AMs following Wnt3a treatment.

2021-05-05 | GSE164791 | GEO

Gene expression in gamma-glutamylcyclotransferase-depleted human prostate cancer PC3 cells.

Project description:Although hypoxia inducible factor-1a (HIF-1a) was originally identified as a transcriptional factor to adapt hypoxia, HIF-1a has also been shown to regulate metabolic pathways specific for cancer, including aerobic glycolysis, namely “Warburg effect”. However, the mechanisms by which HIF-1a mediates the metabolic pathway under normoxia are not fully understood. Here, we identified gamma-glutamylcyclotransferase (GGCT) as a novel regulator of HIF-1a. GGCT is a highly expressed protein in various cancer tissues. Knockdown of GGCT exerts anticancer effects both in vitro and in vivo; thus, it is considered a promising therapeutic target. In this study, we show that depleting GGCT downregulates the protein and mRNA expressions of HIF-1a in PC3 prostate cancer cells, and that overexpressing GGCT upregulates them in mouse fibroblast NIH3T3 cells. We also show that depleting GGCT downregulates HIF-1a downstream target genes involved in glycolysis, whereas overexpressing GGCT exhibits upregulation pattern in these genes. Furthermore, we suggest that GGCT induces the metabolic switch from citric acid cycle to glycolysis under normoxia. Additionally, we show that GGCT regulates expression of HIF-1a protein via AMPK-mTORC1-4EBP1 pathway in PC3 cells. These results indicate the GGCT plays a regulatory role in the expression of HIF-1a followed by glycolytic switch in cancer cells.

2020-07-17 | GSE154584 | GEO

Gene expression in gamma-glutamylcyclotransferase-overexpressing mouse embryonic fibroblast NIH3T3 cells.

2020-07-17 | GSE154592 | GEO