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Multi-dimensional histone modifications for coordinated regulation of gene expression under hypoxia or clioquinol (CQ) treatment.

ABSTRACT: Clioquinol (CQ) has been identified as a hypoxic mimicker to activate hypoxia-inducible factor-1α (HIF-1α) by inhibiting HIF-1a specific asparaginyl hypoxylase (Factor inhibiting HIF-1, FIH-1). We previously showed that hypoxia coordinately regulate induction or repression of hypoxia-responsive genes by altering different types of methylations (H3K4me3, H3K9me3, and H3K27me3) at gene level. Here, we investigated CQ-mediated regulation of the three histone methylations and whether CQ had a similar effect on histone methylation and transcription of target genes under hypoxia.

ORGANISM(S): Homo sapiens

PROVIDER: GSE176379 | GEO | 2022/05/25

REPOSITORIES: GEO

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Multi-dimensional histone modifications for coordinated regulation of gene expression under hypoxia or clioquinol (CQ) treatment [gene expression]

Project description:Clioquinol (CQ) has been identified as a hypoxic mimicker to activate hypoxia-inducible factor-1α (HIF-1α) by inhibiting HIF-1a specific asparaginyl hypoxylase (Factor inhibiting HIF-1, FIH-1). We previously showed that hypoxia coordinately regulate induction or repression of hypoxia-responsive genes by altering different types of methylations (H3K4me3, H3K9me3, and H3K27me3) at gene level. Here, we investigated CQ-mediated regulation of the expression of hypoxia-responsive genes and whether CQ had a similar effect on histone methylation and transcription of target genes under hypoxia.

2022-05-25 | GSE176557 | GEO

SH-SY5Y cells: DMSO vs. clioquinol

Project description:Transcriptional profiling of human SH-SY5Y neuroblastoma cells comparing DMSO-treated control cells with those treated with 50 microM clioquinol (CQ) for 24 h. Two-condition experiment, DMSO vs. CQ . Biological replicates: 1DMSO, 1 CQ. One replicate per array.

2012-10-01 | E-GEOD-32173 | biostudies-arrayexpress

SH-SY5Y cells: DMSO vs. clioquinol

Project description:Transcriptional profiling of human SH-SY5Y neuroblastoma cells comparing DMSO-treated control cells with those treated with 50 microM clioquinol (CQ) for 24 h.

2012-10-01 | GSE32173 | GEO

Expression data of Saccharomyces cerevisiae treated with clioquinol

Project description:Clioquinol (CQ or iodochlorhydroxyquin, 5-chloro-7-iodo-8-hydroxyquinoline) is a hydrophobic chelator of copper, zinc, and iron. It was extensively used as an antibiotic for the treatment of diarrhea and skin infection in the mid-1900s, but then withdrawn because it was reported to be associated with subacute myelo-optic neuropathy (SMON) in Japan. Interest in this drug was recently revived as it was shown that CQ specifically kills cancer cells and significantly decreases Abeta level. Nevertheless, the underlying mechanisms of CQ drug effects and side effects are still unclear. We used yeast, Saccharomyces cerevisiae, as a model to study how CQ affects molecular and cellular functions. Genechip analysis was utilized to examine the effect of CQ on gene expression at the genomic level. To study gene expression profiles of yeast treated with CQ, yeast cells were treated with CQ or DMSO for 5 hours and RNAs were extracted for microarray analysis.

2010-06-08 | E-GEOD-17257 | biostudies-arrayexpress

Expression data of Saccharomyces cerevisiae treated with clioquinol

Project description:Clioquinol (CQ or iodochlorhydroxyquin, 5-chloro-7-iodo-8-hydroxyquinoline) is a hydrophobic chelator of copper, zinc, and iron. It was extensively used as an antibiotic for the treatment of diarrhea and skin infection in the mid-1900s, but then withdrawn because it was reported to be associated with subacute myelo-optic neuropathy (SMON) in Japan. Interest in this drug was recently revived as it was shown that CQ specifically kills cancer cells and significantly decreases Aβ level. Nevertheless, the underlying mechanisms of CQ’s drug effects and side effects are still unclear. We used yeast, Saccharomyces cerevisiae, as a model to study how CQ affects molecular and cellular functions. Genechip analysis was utilized to examine the effect of CQ on gene expression at the genomic level.

2010-05-21 | GSE17257 | GEO

Multi-dimensional histone modifications for coordinated regulation of gene expression under hypoxia or clioquinol (CQ) treatment.

Project description:Multi-dimensional histone modifications for coordinated regulation of gene expression under hypoxia or clioquinol (CQ) treatment.

| PRJNA736037 | ENA

Multi-dimensional histone modifications for coordinated regulation of gene expression under hypoxia or clioquinol (CQ) treatment [gene expression]

Project description:Multi-dimensional histone modifications for coordinated regulation of gene expression under hypoxia or clioquinol (CQ) treatment [gene expression]

| PRJNA736698 | ENA

Determining the hydroxylation status of NAA10-Trp38

Project description:NAA10 is the major human N-terminal acetyltransferase (NAT). The KAT activity of NAA10 towards hypoxia-inducible factor 1α (HIF-1α) was recently reported to depend on the hydroxylation at Trp38 of NAA10 by factor inhibiting HIF-1α (FIH). As a consequence, Trp38 hydroxylation status was proposed to act as a general NAA10-switch between its NAT and KAT state. We attempted to quantify the degree of hydroxylation of NAA10. We could not detect any hydroxylation of Trp38 of NAA10 in several human cell lines.

2022-02-16 | PXD023655 | Pride

Metronomic doxorubicin blocks HIF-1α-mediated responses in sarcomas and augments the effects of anti-VEGF-A therapy

Project description:Increased levels of hypoxia and hypoxia inducible factor 1α (HIF-1α) in human sarcomas correlate with tumor progression and radiation resistance. Prolonged anti-angiogenic therapy of tumors can delay tumor growth but may also increase hypoxia and HIF-1α activity. In our recent clinical trial, treatment with the anti-vascular endothelial growth factor A (VEGF-A) antibody, bevacizumab, followed by a combination of bevacizumab and radiation led to near complete necrosis in nearly half of sarcomas. Gene set enrichment analysis of microarrays from pre-treatment biopsies found the Gene Ontology category “Response to hypoxia” was upregulated in poor responders, and hierarchical clustering based on 140 hypoxia-responsive genes separated poor responders from good responders. The most commonly used chemotherapeutic drug for sarcomas, doxorubicin (Dox), was recently found to block HIF-1α binding to DNA at low metronomic doses. We thus examined Dox treatment in 4 sarcoma cell lines, and found Dox at low concentrations (1-10 uM) blocked HIF-1α induction of VEGF-A by 84-97%, while inhibition of other HIF-1α-target genes including CA9, c-Met and FOXM1 was variable. HT1080 sarcoma xenografts had increased hypoxia and/or HIF-1α activity with increasing tumor size and with anti-VEGF receptor antibody (DC101) treatment. Combining DC101 and metronomic Dox had a synergistic effect in suppressing growth of HT1080 xenografts, primarily via induction of tumor endothelial cell apoptosis. In conclusion, sarcomas respond to increased hypoxia by expressing HIF-1α-target genes which may promote resistance to anti-angiogenic and other therapies. Metronomic Dox can block HIF-1α activation of target genes and works synergistically with anti-VEGF therapy to inhibit sarcomas. Pre-treatment biopsies were collected from 16 human sarcoma. The gene expression analysis was performed using Illumina platform.

2011-08-29 | E-GEOD-31715 | biostudies-arrayexpress

Effect of NDRG3 or HIF-1α knockdown on cell response to hypoxia

Project description:Analysis of Huh-7 hepatocarcinoma cell line depleted of NDRG3 or HIF-1α under hypoxic condition. HIF-1α and NDRG3 have distinct functions in hypoxia responses. Results provide insight into molecular basis of HIF-independent signaling in the development and progression of hypoxic tumors Gene expression profiles of Huh-7 cells stably expressing NDRG3-shRNA or HIF-1α-shRNA under normoxia were compared to gene expression profiles of Huh-7 stable cells under hypoxia for 6, 12 and 24 hours.

2015-07-24 | E-GEOD-55212 | biostudies-arrayexpress

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