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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2019

Open Access 01-12-2019 | Neuroblastoma | Research article

HIF-1 transcription activity: HIF1A driven response in normoxia and in hypoxia

Authors: Flora Cimmino, Marianna Avitabile, Vito Alessandro Lasorsa, Annalaura Montella, Lucia Pezone, Sueva Cantalupo, Feliciano Visconte, Maria Valeria Corrias, Achille Iolascon, Mario Capasso

Published in: BMC Medical Genetics | Issue 1/2019

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Abstract

Background

HIF1A (Hypoxia-Inducible-Factor 1A) expression in solid tumors is relevant to establish resistance to therapeutic approaches. The use of compounds direct against hypoxia signaling and HIF1A does not show clinical efficiency because of changeable oxygen concentrations in solid tumor areas. The identification of HIF1A targets expressed in both normoxia and hypoxia and of HIF1A/hypoxia signatures might meliorate the prognostic stratification and therapeutic successes in patients with high-risk solid tumors.

Methods

In this study, we conducted a combined analysis of RNA expression and DNA methylation of neuroblastoma cells silenced or unsilenced for HIF1A expression, grown in normoxia and hypoxia conditions.

Results

The analysis of pathways highlights HIF-1 (heterodimeric transcription factor 1) activity in normoxia in metabolic process and HIF-1 activity in hypoxia in neuronal differentiation process. HIF1A driven transcriptional response in hypoxia depends on epigenetic control at DNA methylation status of gene regulatory regions. Furthermore, low oxygen levels generate HIF1A-dependent or HIF1A-independent signatures, able to stratify patients according to risk categories.

Conclusions

These findings may help to understand the molecular mechanisms by which low oxygen levels reshape gene signatures and provide new direction for hypoxia targeting in solid tumor.
Appendix
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Metadata
Title
HIF-1 transcription activity: HIF1A driven response in normoxia and in hypoxia
Authors
Flora Cimmino
Marianna Avitabile
Vito Alessandro Lasorsa
Annalaura Montella
Lucia Pezone
Sueva Cantalupo
Feliciano Visconte
Maria Valeria Corrias
Achille Iolascon
Mario Capasso
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2019
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-019-0767-1

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