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Effects of DNA topoisomerase inhibitor acriflavine on endothelial gene expression under hypoxic conditions

ABSTRACT: Effects of DNA topoisomerase inhibitor acriflavine on endothelial gene expression under hypoxic conditions

PROVIDER: PRJNA773246 | ENA |

REPOSITORIES: ENA

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Effects of DNA topoisomerase inhibitor acriflavine on endothelial gene expression under hypoxic conditions

Project description:RNA-Seq of human endothelial cells treated with acriflavine (ACF) with or without hypoxia revealed massive changes on gene expression. These were non-randomly and potentially due to DNA topoisomerase inhibition rather than HIF inhibition. Surprisingly, in contrast to protein-coding genes, RNA-Seq yielded that an exceeding number of lncRNAs is upregulated.

2022-01-19 | GSE186297 | GEO

Effects of DNA topoisomerase inhibitor acriflavine on endothelial gene expression and chromatin accessibility

Project description:Effects of DNA topoisomerase inhibitor acriflavine on endothelial gene expression and chromatin accessibility

| PRJNA736692 | ENA

Effects of DNA topoisomerase inhibitor acriflavine on endothelial gene expression and chromatin accessibility (RNA-Seq)

Project description:Effects of DNA topoisomerase inhibitor acriflavine on endothelial gene expression and chromatin accessibility (RNA-Seq)

| PRJNA736696 | ENA

Effects of DNA topoisomerase inhibitor acriflavine on endothelial gene expression and chromatin accessibility (ATAC-Seq)

Project description:Effects of DNA topoisomerase inhibitor acriflavine on endothelial gene expression and chromatin accessibility (ATAC-Seq)

| PRJNA736697 | ENA

Effects of DNA topoisomerase inhibitor acriflavine on endothelial gene expression and chromatin accessibility (RNA-Seq)

Project description:RNA-Seq of human endothelial cells treated with ACF revealed massive changes on gene expression. These were non-randomly and strongly conserved to murine lung endothelial cells potentially due to DNA topoisomerase inhibition rather than HIF inhibition. Surprisingly, in contrast to protein-coding genes, RNA-Seq yielded that an exceeding number of lncRNAs is upregulated, e.g. FENDRR, H19, HIF1α-AS1 and FLJ31356, whereas BOLA3-AS1 and MEG3 were strongly downregulated. ATAC-Seq demonstrated that ACF leads to strong changes on chromatin accessibility on lncRNA promoters.

2022-01-19 | GSE176555 | GEO

Effects of DNA topoisomerase inhibitor acriflavine on endothelial gene expression and chromatin accessibility (ATAC-Seq)

2022-01-19 | GSE176554 | GEO

Acriflavine, a Potent Inhibitor of HIF-1α, Disturbs Glucose Metabolism and Suppresses ATF4-Protective Pathways in Melanoma under Non-Hypoxic Conditions.

Project description:Hypoxia-inducible factor (HIF)-1α is constitutively expressed in melanoma cells under normoxic conditions and its elevated expression correlates with the aggressiveness of melanoma tumors. Here, we used acriflavine, a potent inhibitor of HIF-1α dimerization, as a tool to investigate whether HIF-1α-regulated pathways contribute to the growth of melanoma cells under normoxia. We observed that acriflavine differentially modulated HIF-1α-regulated targets in melanoma under normoxic conditions, although acriflavine treatment resulted in over-expression of vascular endothelial growth factor (VEGF), its action clearly downregulated the expression of pyruvate dehydrogenase kinase 1 (PDK1), a well-known target of HIF-1α. Consequently, downregulation of PDK1 by acrifavine resulted in reduced glucose availability and suppression of the Warburg effect in melanoma cells. In addition, by inhibiting the AKT and RSK2 phosphorylation, acriflavine also avoided protective pathways necessary for survival under conditions of oxidative stress. Interestingly, we show that acriflavine targets activating transcription factor 4 (ATF4) for proteasomal degradation while suppressing the expression of microphthalmia-associated transcription factor (MITF), a master regulator of melanocyte development and a melanoma oncogene. Since acriflavine treatment results in the consistent death of melanoma cells, our results suggest that inhibition of HIF-1α function in melanoma could open new avenues for the treatment of this deadly disease regardless of the hypoxic condition of the tumor.

| S-EPMC7795823 | biostudies-literature

Aspergillus CEA10 compared to SRBA mutant under hypoxic conditions

Project description:Aspergillus fumigatus strains CEA10 and srbA mutant expression patterns were compared after exposure to 24h of hypoxic conditions Goal of this study was to find genes that are directly and/or indirectly regulated by the transcription factor srbA, that is know to be crucial for growth under hypoxic conditions Keywords: hypoxic stress response

2008-10-15 | GSE12376 | GEO

Aspergillus CEA10 compared to SRBA mutant under hypoxic conditions

2010-05-18 | E-GEOD-12376 | biostudies-arrayexpress

Differential expressions of microRNAs under normoxic and hypoxic conditions

Project description:Outcome prediction classifiers were successfully constructed through expression profiling of a total of 1,329 miRNAs in MKN1, gastric cancer cell line under normoxic and hypoxic conditions.

2014-04-18 | GSE56870 | GEO

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