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.

Details

Title
HIF-1 transcription activity: HIF1A driven response in normoxia and in hypoxia
Author
Cimmino, Flora; Avitabile, Marianna; Lasorsa, Vito Alessandro; Montella, Annalaura; Pezone, Lucia; Cantalupo, Sueva; Visconte, Feliciano; Corrias, Maria Valeria; Iolascon, Achille; Capasso, Mario
Publication year
2019
Publication date
2019
Publisher
BioMed Central
e-ISSN
14712350
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2193707532
Copyright
Copyright © 2019. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.