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Homo sapiens

ABSTRACT: Chip-Seq analysis of HAUSP and HIF-1alpha

PROVIDER: PRJNA308565 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR3098450.fastq.gz	Fastqsanger.gz
	SRR3098451.fastq.gz	Fastqsanger.gz
	SRR3098452.fastq.gz	Fastqsanger.gz
	SRR3098453.fastq.gz	Fastqsanger.gz

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Homo sapiens

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Project description:DNA Topoisomerase I inhibition by Camptothecin (CPT) derivatives can impair the hypoxia-induced cell transcriptional response. In the present work, we determined molecular aspects of the mechanism of CPT effects on HIF-1alpha activity in human cancer cells. In particular, we provide evidence that low concentrations of CPT, without interfering with HIF-1alpha mRNA levels, can reduce HIF-1alpha protein expression and activity. As luciferase assays demonstrated the involvement of the HIF-1alpha mRNA 3M-^RUTR in CPT-induced impairment of HIF-1alpha protein regulation, we performed microarray analysis to identify CPT-induced modification of miRNAs targeting HIF-1alpha mRNA under hypoxic-mimetic conditions. The selected miRNAs were then further analyzed demonstrating a role for miR-17-5p and miR-155 in HIF-1alpha protein expression after CPT treatments. The present findings establish miRNAs as key factors in a molecular pathway connecting Top1 inhibition and human HIF-1alpha protein regulation and activity, widening the biological and molecular activity of CPT derivatives and the perspective for novel clinical interventions.

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