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Expression data from ovarian cancer cell lines

ABSTRACT: Ovarian clear cell carcinoma (OCCC) shows unique clinical features including an association with endometriosis and poor prognosis. We previously reported that the contents of endometriotic cysts, especially high concentrations of free iron, are a possible cause of OCCC carcinogenesis through iron-induced persistent oxidative stress. In this study, we conducted gene expression microarray analysis using 38 ovarian cancer cell lines and identified genes commonly expressed in both OCCC cell lines and clinical samples, which comprise an OCCC gene signature. The OCCC signature reproducibly predicts OCCC specimens in other microarray data sets, suggesting that this gene profile reflects the inherent biological characteristics of OCCC. The OCCC signature contains known markers of OCCC, such as hepatocyte nuclear factor-1b (HNF-1b) and versican (VCAN), and other genes that reflect oxidative stress. Expression of OCCC signature genes was induced by treatment of immortalized ovarian surface epithelial cells with the contents of endometriotic cysts, indicating that the OCCC signature is largely dependent on the tumor microenvironment. Induction of OCCC signature genes is at least in part epigenetically regulated, as we found hypomethylation of HNF-1b and VCAN in OCCC cell lines. This genomewide study indicates that the tumor microenvironment induces specific gene expression profiles that contribute to the development of distinct cancer subtypes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE29175 | GEO | 2011/05/16

SECONDARY ACCESSION(S): PRJNA139981

REPOSITORIES: GEO

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Expression data from ovarian cancer cell lines

Project description:Ovarian clear cell carcinoma (OCCC) shows unique clinical features including an association with endometriosis and poor prognosis. We previously reported that the contents of endometriotic cysts, especially high concentrations of free iron, are a possible cause of OCCC carcinogenesis through iron-induced persistent oxidative stress. In this study, we conducted gene expression microarray analysis using 38 ovarian cancer cell lines and identified genes commonly expressed in both OCCC cell lines and clinical samples, which comprise an OCCC gene signature. The OCCC signature reproducibly predicts OCCC specimens in other microarray data sets, suggesting that this gene profile reflects the inherent biological characteristics of OCCC. The OCCC signature contains known markers of OCCC, such as hepatocyte nuclear factor-1b (HNF-1b) and versican (VCAN), and other genes that reflect oxidative stress. Expression of OCCC signature genes was induced by treatment of immortalized ovarian surface epithelial cells with the contents of endometriotic cysts, indicating that the OCCC signature is largely dependent on the tumor microenvironment. Induction of OCCC signature genes is at least in part epigenetically regulated, as we found hypomethylation of HNF-1b and VCAN in OCCC cell lines. This genomewide study indicates that the tumor microenvironment induces specific gene expression profiles that contribute to the development of distinct cancer subtypes. Affymetrix Human Genome U133A 2.0 Array was conducted for 38 ovarian cancer cell lines (13 OCCC cell lines and 25 non-OCCC cell lines). All specimens were arrayed in parallel and used for RMA normalization.

2011-05-16 | E-GEOD-29175 | biostudies-arrayexpress

Expression Data from HNF1b-knockdown RMG2-ovarian cancer cells

2012-05-01 | GSE37290 | GEO

Expression Data from HNF1b-knockdown RMG2-ovarian cancer cells

Project description:Ovarian clear cell carcinoma (OCCC) is a morphologically and biologically distinct subtype of ovarian carcinomas. We previously reported a gene expression profile characteristic of OCCC (OCCC signature), which contains hepatocyte nuclear facter-1b ( HNF-1b). To elucidate the biological role of HNF-1b in OCCC, we performed the suppression of the HNF-1b expression in human ovarian cancer cell line RMG2 using short hairpin RNA. We are now evaluating the functional effect using these cells. Affimetrix Human Genome U133A plus 2.0 chips was conducted for HNF1b knockdown and non-silencing cells (five replicates each for RMG2-HNF1b-sh1 and RMG2-HNF1b-sh2, ten replicates for the RMG2-control). All specimens were arrayed in parallel and used for RMA normalization.

2012-04-30 | E-GEOD-37290 | biostudies-arrayexpress

Transcriptome analysis of endometriotic stromal cells treated with hydrogen peroxide

Project description:In ovarian endometrioma, much iron, which is derived from blood in cyst, deposit in stroma. This iron generates oxidative stress by Fenton reaction, which is supposed to affect endometriotic stromal cells. We used gene expression microarrays to find influence of oxidative stress on endometriotic stromal cells. Gene expression microarrays revealed no statistically differences caused by oxidative stress.

2012-06-04 | GSE31515 | GEO

The phosphate exporter XPR1/SLC53A1 is required for the tumorigenicity of ovarian cancer.

Project description:Ovarian cancer is the fifth cause of cancer-related death in women. Ovarian clear cell carcinoma (OCCC) is a chemotherapy-resistant epithelial ovarian cancer with poor prognosis. As a basis for the development of therapeutic agents that may improve the prognosis of OCCC, we performed a screen for proteins critical for the tumorigenicity of OCCC using the CRISPR/Cas9 system. Here we show that knockdown of the phosphate exporter XPR1/SLC53A1 induces the growth arrest and apoptosis of OCCC cells in vitro. Moreover, we demonstrate that knockdown of XPR1/SLC53A1 inhibits the proliferation of OCCC cells xenografted into immunocompromised mice. These results suggest that XPR1/SLC53A1 plays a critical role in the tumorigenesis of OCCC cells. We speculate that XPR1/SLC53A1 might be a promising molecular target for the therapeutic treatment of OCCC.

2022-07-07 | GSE189552 | GEO

Gene expression profiling of epithelial ovarian cancer by bulk RNA-seq

Project description:Ovarian cancer has one of the worst prognoses among gynecologic malignancies. About 60% of ovarian cancer cases are diagnosed at Stages III and IV, and their five-year survival rate is less than 30%. Ovarian cancer is classified into four major histological subtypes; serous, clear cell, endometrioid and mucinous. Ovarian clear cell carcinoma (OCCC) is less sensitive to conventional platinum-based chemotherapy and has worse prognosis than other subtypes. In this study, we attempted to identify novel molecular targets critical for the proliferation and tumorigenicity of OCCC using the CRISPR/Cas9 system, and identified some genes as important candidates. Some of these candedates were upregulated in ovarian cancer tissue, especially OCCC. Our results suggest that not only may be these candedates a promising diagnostic maker for OCCC, drugs against these candedates would be useful for the therapeutic treatment of OCCC.

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Hnf-1β ChIP-Seq

Project description:Genome Wide mapping of Hnf-1β in kidney cells. Tissue-specific transcription factor that is expressed in the kidney and other epithelial organs. Humans with mutations in HNF1? develop kidney cysts, and HNF-1β regulates the transcription of several cystic disease genes. However, the complete spectrum of HNF-1β-regulated genes and pathways is not known. Here, we used ChIP-seq and DNA microarray analysis to identify 1,545 protein-coding genes that are directly regulated by HNF-1β in kidney epithelial cells. Pathway analysis predicted that HNF-1β regulates cholesterol metabolism. The expression of genes that are essential for cholesterol synthesis, including Srebf2 and Hmgcr, was reduced by expression of dominant-negative mutant HNF-1β or kidney-specific inactivation of HNF-1β. The levels of cholesterol biosynthetic intermediates and the rate of cholesterol synthesis were decreased in HNF-1β mutant cells. In addition, HNF-1β directly regulated the renal epithelial expression of PCSK9, a key regulator of cholesterol uptake, and depletion of cholesterol in the culture medium mitigated the inhibitory effects of mutant HNF-1β on SREBP-2 and HMGCR. These findings reveal a novel role of HNF-1β in regulating multiple steps in renal cholesterol metabolism.

2015-08-15 | GSE71250 | GEO

Inactivation of transcription factor HNF-1β with CRISPR/Cas9 induces epithelial-mesenchymal transition

Project description:Hepatocyte nuclear factor-1β (HNF-1β) is a tissue-specific transcription factor that is essential for the development of the kidney. Mutations of HNF-1β produce autosomal dominant tubulointerstitial kidney disease (ADTKD) characterized by tubular cysts, renal fibrosis, and progressive decline in kidney function. To understand the functions of HNF-1β, we generated HNF-1β-deficient mIMCD3 renal epithelial cells. Gene editing with CRISPR/Cas9 was used to delete exon 1 of HNF-1β by non-homologous end joining (NHEJ). We performed RNA-seq on three independent HNF-1β-deficient mIMCD3 cell lines and three paired control cell lines. Our RNA-seq of HNF-1β-deficient cells showed upregulation of 1,135 genes and repression of 759 genes compared to control cells. Pathway analysis revealed that fibrosis and epithelial-mesenchymal transition (EMT) pathways were highly activated in HNF-1β-deficient cells. We conclude that loss of HNF-1β in renal epithelial cells leads to the activation of a transcriptional network that induces EMT and aberrant TGFβ signaling. Targeting this network may inhibit fibrosis in ADTKD and other chronic kidney diseases.

2018-08-10 | GSE97770 | GEO

The splicing factor DHX38/PRP16 is required for ovarian clear cell carcinoma tumorigenesis, as revealed by a CRISPR-Cas9 screen

Project description:Certain cancers, such as ovarian clear cell carcinoma (OCCC), display high levels of genetic variation between patients, confounding the development of effective therapies. In order to identify novel genes critical to OCCC growth, we employed the pooled genome-scale CRISPR Knock-Out (GeCKO) v2 CRISPR-Cas9 knockout screening system using the OCCC cell line JHOC5, as well as the T-antigen immortalized normal ovarian surface epithelium cell line OSE3 as a negative control. We identified the gene encoding DHX38/PRP16, an ATP-dependent RNA helicase involved in splicing, as critical for the growth and tumorigenesis of OCCC; DHX38 knockdown in OCCC cells, but not normal cells, induces apoptosis and impairs OCCC tumorigenesis in a mouse model. Our results suggest that DHX38/PRP16 may play a role in OCCC tumorigenesis, and can be regarded as a promising therapeutic target.

2022-01-19 | GSE188485 | GEO

A genome-wide CRISPR/Cas9 screen identifies therapeutic targets required for the tumorigenesis of ovarian clear cell carcinoma (OCCC).

Project description:To identify genes critical for the proliferation of ovarian clear cell carcinoma (OCCC), we performed CRISPR/CAS9 screens against the OCCC cell lines OVICE, ES2, TOV21G and JHOC5 using the TKOv3 sgRNA library.

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