CHD1 deletion stabilizes HIF1α to promote angiogenesis and glycolysis in prostate cancer / 亚洲男科学杂志(英文版)
Asian Journal of Andrology
;
(6): 152-157, 2023.
Article
Dans Anglais
| WPRIM
| ID: wpr-971026
ABSTRACT
Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Tumeurs de la prostate
/
Helicase
/
Lignée cellulaire tumorale
/
Protéines de liaison à l'ADN
/
Protéine Von Hippel-Lindau supresseur de tumeur
/
Sous-unité alpha du facteur-1 induit par l'hypoxie
/
Prolyl hydroxylases
/
Glycolyse
/
Hypoxie
Limites du sujet:
Humains
/
Mâle
langue:
Anglais
Texte intégral:
Asian Journal of Andrology
Année:
2023
Type:
Article
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