Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

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.

2024-07-29 | GSE267703 | GEO

Effects of deletion of SAT1, a polyamine-metabolic enzyme, on mouse HeLa xenograft tumor

Project description:An acidic tumor microenvironment plays a critical role in tumor progression. However, understanding of metabolic reprogramming of tumors in response to acidic extracellular pH has remained elusive. Using comprehensive metabolomic analyses, we demonstrated that acidic extracellular pH (pH 6.8) leads to the accumulation of N1-acetylspermidine, a pro-tumor metabolite, through upregulation of the expression of spermidine/spermine acetyl transferase 1 (SAT1). Inhibition of SAT1 expression suppressed the accumulation of intra- and extracellular N1-acetylspermidine at acidic pH. Conversely, overexpression 3 of SAT1 increased intra- and extracellular N1-acetylspermidine levels, supporting the proposal that SAT1 is responsible for accumulation of N1-acetylspermidine. While inhibition of SAT1 expression only had a minor effect on cancer cell growth in vitro, SAT1 knockdown significantly decreased tumor growth in vivo, supporting a contribution of the SAT1-N1-acetylspermidine axis to pro-tumor immunity. Immune cell profiling revealed that inhibition of SAT1 expression decreased neutrophil recruitment to the tumor, resulting in impaired angiogenesis and tumor growth. We showed that anti-neutrophil neutralizing antibodies suppressed growth in control tumors to a similar extent to that seen in SAT1 knockdown tumors in vivo. Further, a SAT1 signature was found to be correlated with poor patient prognosis. Our findings demonstrate that extracellular acidity stimulates recruitment of pro-tumor neutrophils via the SAT1-N1-acetylspermidine axis, which may represent a novel target for anti-tumor immune therapy.

2023-08-14 | GSE239784 | GEO

Identification of SAT1 regulated genes in GBM cells by microarray

Project description:We aimed to identify SAT1 regulated genes in U87MG cell by knockdown of SAT1 with two different shRNAs, and then compared knockdown cells to control cells with shGFP

2021-06-23 | GSE116395 | GEO

Genes regulated by SAT1 in brain tumors

Project description:Performed gene expression profiling of U87MG cells with two different shRNAs to SAT1 using Affymetrix microarrays covering 67,528 gene transcripts. Accordingly, we infected U87MG cells with lentiviruses expressing shRNAs to either the green fluorescent protein (GFP) or SAT1, performed a drug selection to ensure stable expression of the shRNAs, and expanded the cells for RNA harvest within 7 days of infection. RNA was reverse transcribed into cDNA, labelled with biotin and hybridized onto the arrays for analyses. Hierarchical clustering of duplicate experiments correctly segregated samples according to sample identity (i.e. shGFP clustered together, shSAT1-1 clustered together, and shSAT1-2 clustered together; with the latter two separately branching from shGFP)

2019-09-18 | E-MTAB-7270 | biostudies-arrayexpress

Identification of BCL2A1 as a stress-inducible gene in enhancing ovarian cancer cell survival in hypoxic condition

Project description:The anti-hypoxia capacity of ovarian cancer cells leads survive in stress tumor microenvironment intraperitoneal cavity. The identification of putative stress-induced factors may be used as target genes to impair the peritoneal metastases in ovarian cancer. In this study, a pool of ovarian cancer cells was treated by hypoxia (0.5% O2, 5% CO2, 24 h) or normoxia. Using transcriptional profiling (GeneChipTM Affymetrix Human Genome U133 Plus 2.0 Array) analysis, we identified BCL2A1 was a putative target gene protecting ovarian cancer cells against numerous stresses.

2020-10-28 | E-MTAB-9730 | biostudies-arrayexpress

Streptomyces sp. SAT1

Project description:Streptomyces sp. SAT1 Genome sequencing and assembly

| PRJNA321638 | ENA

Histone H3K27me3 demethylase act as a regulator of stemness in hypoxic cancer cells that are detached from extracellular matrix

Project description:Metastasis of cancer cells requires detachment from Extra Cellular Matrix (ECM) to seed cancer cells in a distant organ. Hypoxia is prevalent in this matrix detached cancer cells. Studies have established hypoxia as a chromatin modifier, as it transcriptionally controls expression of various histone demethylases (KDMs); therefore, we hypothesized that the presence of hypoxia could modulate the expression of KDMs in matrix detached cancer cells. Our study showed that in matrix detached cancer cells, both hypoxia and one of the hypoxia regulated H3K27me3 histone demethylase, namely KDM6B, was increased. Simultaneously, we found increased expression of stemness-associated genes, namely SOX-2, SOX-9, and CD44, in hypoxic matrix detached cancer cells. We discovered that KDM6B occupies the promoter region of both SOX-2 and CD44 to regulate their expression epigenetically. Targeting KDM6B reduces its occupancy, thereby expressing the stemness-related genes in matrix detached cancer cells. Further, we noticed increased occupancy of HIF1α promoter by KDM6B, suggesting its regulatory role in maintaining hypoxia in matrix detached cancer cells. This observation was further strengthened as we found a significant positive association between KDM6B and HIF1α in various cancer types. Overall, we found that matrix detachment modulates epigenome by inducing KDM6B activity to regulate the expression of stemness-related genes and hypoxia primarily through HIF1α in matrix detached conditions. KDM6B can be developed as a therapeutic target to eliminate matrix detached cancer cells bound for metastatic events

2021-06-11 | GSE176558 | GEO

Ezetimibe derivative L14-8 suppresses advanced prostate cancer by activating PLK1/TP53-SAT1-induced ferroptosis

Project description:Androgen receptor signaling inhibitors (ARSIs) have demonstrated a survival benefit in metastatic prostate cancer (PCa). However, patients taking these agents inevitably acquire resistance and even develop neuroendocrine prostate cancer (NEPC), in which stage, the AR signaling is inactive, and therapies are limited for these lethal cases. Therefore, there is an urgent need to develop novel treatments to improve patient outcomes. Here we report that L14-8, a small molecule derived and optimized from ezetimibe, significantly suppressed prostate cancer growth by inducing ferroptosis in vitro and in vivo without obvious toxicity. Further mechanism studies demonstrate that L14-8 bound to and enhanced the stability of PLK1 and promoted the phosphorylation and expression of TP53, which enhanced its enrichment at the promoter of SAT1, a ferroptosis inducer, and increased its transcriptional activity. Overall, our studies developed a novel anti-tumor agent for treating lethal prostate cancer in an AR-independent manner and provided mechanistic insights into its action by targeting the PLK1-mediated TP53-SAT1 axis-induced ferroptosis.

2024-09-17 | GSE276906 | GEO

Candidatus Nitrosotenuis cloacae strain:SAT1

Project description:Candidatus Nitrosotenuis cloacae strain:SAT1 Genome sequencing

| PRJNA272771 | ENA

Comparative proteomics of dying and surviving cancer cells improves the identification of drug targets and sheds light on cell life/death decisions

Project description:Chemotherapeutics cause the detachment and death of adherent cancer cells. When studying the proteome changes to determine the protein target and mechanism of action of anticancer drugs, the still-attached cells are normally used, while the detached cells are usually ignored. Here we tested the hypothesis that proteomes of detached cells contain valuable information and therefore separately analyzed the proteomes of detached and attached HCT-116, A375 and RKO cells obtained 48 h after treatment with 5-fluorouracil, methotrexate and paclitaxel. Combined proteome data provided a more accurate identification of drug targets. Six proteins consistently up- or down-regulated in the detached vs attached cells regardless of the drug and cell type were targeted by siRNA. Knocking down USP11, CTTN, ACAA2 and EIF4H had anti-proliferative effects, targeting UHRF1 additionally sensitized the cells to the anticancer drugs, while knocking down RNF-40 increased cell survival against the treatments. Therefore, these proteins are likely to be involved in general cell death and survival decisions. Adding detached cells to the analysis could become a standard practice in expression proteomics of drug-treated cells.

2018-03-28 | PXD007686 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data