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Effect of detachment culture condition and depletion of SAT1 on gene expression in SKOV3 ovarian cancer cell line

ABSTRACT: Ovarian cancer is an aggressive malignancy characterized by the ascitic fluid and peritoneal metastases. Cancer cells detach from the extracellular matrix and survives the loss of anchorage in the ascites to disseminate extensively in the peritoneal cavity. Metabolic reprogramming is often observed in the cancer progression, yet its role in peritoneal metastasis is largely unexplored. Here we report that spermidine/spermine N1-acetyltransferase 1 (SAT1) promotes the anchorage-independent cell survival and potentiates metastatic dissemination. We compared the detached vs attached cells with RNAseq and identified that hypoxia was among the most enriched pathways using gene set enrichment analysis.To define the underlying mechanism, we first carried out RNA-seq analysis of the detached ovarian cancer cells with or without knocking down SAT1 and identified 1,829 differentially expressed genes (P value < 0.05) in the detached SAT1 knocking down cells. Gene Ontology (GO) term enrichment analysis recognized the differentially expressed genes associated extensively with mitotic process, most likely reflecting a role of SAT1 in cell cycle control. Taken together, our data suggest that SAT1 was induced by hypoxia in the detached cell and played an important role in cell cycle control.

ORGANISM(S): Homo sapiens

PROVIDER: GSE267614 | GEO | 2024/07/29

REPOSITORIES: GEO

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Effect of SAT1 depletion on H3K27ac alterations in the ovarian cancer cell line SKOV3 in detached conditions by chromatin immunoprecipitation and sequencing (ChIP-seq) analysis

Project description:Ovarian cancer is an aggressive malignancy characterized by the ascitic fluid and peritoneal metastases. Cancer cells detach from the extracellular matrix and survives the loss of anchorage in the ascites to disseminate extensively in the peritoneal cavity. Metabolic reprogramming is often observed in the cancer progression, yet its role in peritoneal metastasis is largely unexplored. Here we report that spermidine/spermine N1-acetyltransferase 1 (SAT1) promotes the anchorage-independent cell survival and potentiates metastatic dissemination. Analysis of different histone modifications in the SAT1-depleted ovarian cancer cells upon detachment revealed only a dramatic reduction in the level of H3K27ac, whereas the levels of 15 other histone lysine modifications were not reduced or slightly affected. Chromatin immunoprecipitation and sequencing (ChIP-seq) analysis of H3K27ac to map gene regions with significantly altered H3K27ac identified 1870 genes with increased and 1556 genes with reduced H3K27ac peaks in SAT1-deficient ovarian cancer cells compared to control cells upon detachment.Integrated analysis of RNA-seq and H3K27ac ChIP-seq datasets indicated that 11.05% of genes with reduced H3K27ac peaks were transcriptionally down-regulated. Remarkably, such genes were broadly associated with mitotic cell cycle process, chromosome organization, and chromosome segregation.Taking these findings together, we conclude that SAT1 increases H3K27ac mark within genes required for mitosis regulation and chromosome segregation, thereby protecting ovarian cancer cells from mitotic catastrophe upon detachment.

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