CHD1 deletion stabilizes HIF1α to promote angiogenesis and glycolysis in prostate cancer.
- Author:
Yu-Zhao WANG
1
;
Yu-Chen QIAN
1
;
Wen-Jie YANG
1
;
Lei-Hong YE
1
;
Guo-Dong GUO
1
;
Wei LV
1
;
Meng-Xi HUAN
1
;
Xiao-Yu FENG
1
;
Ke WANG
1
;
Zhao YANG
1
;
Yang GAO
1
;
Lei LI
1
;
Yu-Le CHEN
1
Author Information
- Publication Type:Journal Article
- Keywords: CHD1; HIF1α; angiogenesis; metabolism; prostate cancer
- MeSH: Male; Humans; Von Hippel-Lindau Tumor Suppressor Protein/metabolism*; DNA-Binding Proteins/metabolism*; Prolyl Hydroxylases/metabolism*; Hypoxia; Prostatic Neoplasms/pathology*; Glycolysis; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*; Cell Line, Tumor; DNA Helicases/metabolism*
- From: Asian Journal of Andrology 2023;25(2):152-157
- CountryChina
- Language:English
- 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.
