RNA-seq analysis of PHD and VHL inhibitors reveals differences and similarities to the hypoxia response.

Wellcome Open Research
Julianty FrostSonia Rocha

Abstract

Background: Hypoxia-inducible factor (HIF) transcription factors are well known to control the transcriptional response to hypoxia. Given the importance of cellular response to hypoxia, a number of pharmacological agents to interfere with this pathway have been developed and entered pre-clinical or clinical trial phases. However, how similar or divergent the transcriptional response elicited by different points of interference in cells is currently unknown. Methods: We performed RNA-sequencing to analyse the similarities and differences of transcriptional response in HeLa cells treated with hypoxia or chemical agents that stabilise HIF by inhibiting components of the hypoxia signalling pathway - prolyl hydroxylase (PHD) inhibitor or von Hippel-Lindau (VHL) inhibitor. Results: This analysis revealed that hypoxia produces the highest changes in gene transcription, with activation and repression of genes being in large numbers. Treatment with the PHD inhibitor IOX2 or the VHL inhibitor VH032 led mostly to gene activation, majorly via a HIF-dependent manner. These results were also confirmed by qRT-PCR using more specific and/or efficient inhibitors, FG-4592 (PHDs) and VH298 (VHL). Conclusion: PHD inhibition and VHL inhibition mimi...Continue Reading

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Citations

Aug 14, 2019·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Jane AchanUmberto D'Alessandro
Jul 10, 2020·Journal of Cellular Physiology·Scott S HannahConor McClean
Jul 16, 2020·Communications Biology·Xiaodong ZhuangJane A McKeating
Jun 27, 2021·The Journal of Biological Chemistry·Julianty FrostAlessio Ciulli

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Datasets Mentioned

BETA
GSE120675

Methods Mentioned

BETA
Genome Sequencing
RNA-seq
Illumina sequencing
RNA seq
ChIP
ChIP-seq
PCR

Software Mentioned

featureCounts pipeline
GSEA
R
Ensembl
TFEA
R package edgeR
subread
STAR
MxPro qPCR
ChIP

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