EZH2 Mediated Metabolic Rewiring Promotes High-grade Serous Ovarian Cancer Progression Independently of Histone Methyltransferase Activity II
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA869742 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21066933_1.fastq.gz | Fastqsanger.gz | |||
| SRR21066933_2.fastq.gz | Fastqsanger.gz | |||
| SRR21066934_1.fastq.gz | Fastqsanger.gz | |||
| SRR21066934_2.fastq.gz | Fastqsanger.gz | |||
| SRR21066935_1.fastq.gz | Fastqsanger.gz |
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Project description:EZH2 Mediated Metabolic Rewiring Promotes High-grade Serous Ovarian Cancer Progression Independently of Histone Methyltransferase Activity
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Project description:Despite EZH2 is overexpressed and exerts an oncogenic role in various cancer through catalytic-dependent or -independent manner, the mechanisms of EZH2 contributing to high-grade serous ovarian cancer (HGSOC) are incompletely understood. Here, we showed that a subgroup of HGSOC patients with high EZH2 expression but low H3K27me3 level exhibited worst prognosis. We demonstrated that EZH2 degradation but not catalytic inhibition profoundly lowered EZH2 protein and blocked cell proliferation and tumorigenicity in vitro and in vivo. Ectopic expression of EZH2 without SET domain (EZH2-∆SET), which is known to be essential for catalytic activity, restored the phenotypes of EZH2 degradation. Mechanistically, we identified that IDH2 was transactivated by EZH2 to impair metabolic rewiring by disrupting the TCA cycle, which contributed to the oncogenic role of EZH2 in OC. Together, these data reveal a novel carcinogenic role of EZH2 in HGSOC, and provide potential strategies in HGSOC by targeting EZH2 non-catalytic activity.
2023-08-11 | GSE185604 | GEO
Project description:Enhancer of zeste homolog 2 (EZH2), the key catalytic subunit of polycomb repressive complex 2 (PRC2), is overexpressed and exerts an oncogenic role in various cancers through catalytic-dependent or -independent pathways. However, the mechanisms contributing to high-grade serous ovarian cancer (HGSOC) are not well understood. Here, we showed that a subgroup of HGSOC patients with high EZH2 expression but low H3K27me3 level exhibited the worst prognosis. We demonstrated that induction of EZH2 degradation but not catalytic inhibition profoundly blocked ovarian cancer cell proliferation and tumorigenicity in vitro and in vivo. We further demonstrated that EZH2 transcriptionally upregulated IDH2 to potentiate metabolic rewiring by enhancing the tricarboxylic acid cycle (TCA cycle), which contributed to the progression of HGSOC. Together, these data reveal a novel oncogenic role of EZH2 in HGSOC, and provide potential therapeutic strategies in HGSOC by targeting EZH2 non-catalytic activity.
2023-08-11 | GSE211307 | GEO
Project description:Rewiring of master transcription factor cistrome during high-grade serous ovarian cancer development
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Project description:Ovarian cancer is the most lethal gynecologic cancer. High-grade serous ovarian carcinoma (HGSOC) is the most common histologic subtype, accounting for three quarters of ovarian cancer. To clarify the changes of gene expression in serous ovarian cancer, we performed lncRNA and mRNA microarrays to identify differentially expressed lncRNAs and mRNAs in High-grade and Low-grade serous ovarian carcinoma compared with Normal fallopian tube.
2020-02-12 | GSE135886 | GEO
Project description:Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed. Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed.
2011-03-04 | GSE27659 | GEO
Project description:Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed. Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed. Gene expression analysis was performed on five serous borderline tumors with BRAF mutation and five serous borderline tumors without BRAF mutation randomly. RNA was extracted from microdissected tumor cells. Expression profiling was carried out with Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays
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Project description:In this study, we performed miRNA profiles analysis of high-grade serous ovarian carcinoma compared to normal fallopian tube fimbria using microarray (Exiqon, Denmark) to evaluate their potential role in the pathogenesis of uterine leiomyoma. miRNA profiling analysis of the 10 samples including 5 high-grade serous ovarian carcinomas and 5 normal fallopian tube fimbria.
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Project description:Low-grade serous ovarian carcinomas are typically Ras-pathway mutated, TP53 wild-type, have limited chromosomal aberration, and are frequently associated with borderline tumors. By contrast, high-grade serous ovarian carcinoma lack Ras-pathway mutations, are invariably TP53 mutated, show widespread genomic change, and are commonly BRCA-pathway disrupted. We sought to identify differences in genomic copy number changes in borderline and invasive components of serous carcinoma.
2014-10-01 | GSE57270 | GEO
Project description:Low-grade serous ovarian carcinomas are typically Ras-pathway mutated, TP53 wild-type, have limited chromosomal aberration, and are frequently associated with borderline tumors. By contrast, high-grade serous ovarian carcinoma lack Ras-pathway mutations, are invariably TP53 mutated, show widespread genomic change, and are commonly BRCA-pathway disrupted. We sought to identify differentially expressed genes between co-existing borderline and invasive components of serous carcinoma.
2014-10-01 | GSE56443 | GEO