Gene expression profiling of prostate cells with CHD1 knockdown
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE33531 | GEO | 2011/12/19
SECONDARY ACCESSION(S): PRJNA148905
REPOSITORIES: GEO
Similar Datasets
Project description:Gene expression profiling of prostate tumor cells comparing cells that have CHD1 knockdown by shRNA (RWPE-1, OPCN2) or siRNA (LNCaP) with cells treated with non-targeted control. Prostate cell lines had CHD1 knockdown via shRNA or siRNA were hybridized against cells that were targeted with non-targeting control. OPCN2 and RWPE-1 RNA were dye-swapped in replicate experiments.
2011-12-19 | E-GEOD-33531 | biostudies-arrayexpress
Project description:We used microarrays to study the global gene expression and identified differentially expressed genes in CHD1 knockdown PC-3 cells and CHD1 KO LNCaP cells, aiming to identify genes and pathways that are regulated by CHD1
2017-02-10 | GSE84970 | GEO
Project description:Next generation androgen receptor (AR) signaling inhibitors have significantly improved the survival of men with metastatic castration-resistant prostate cancer (mCPRC) but resistance remains a problem. Genomic alterations at the AR locus are present in ~50% of mCRPC patients, typically in association with large numbers of copy number gains and losses across the genome. To explore the functional consequences of these copy number alterations, we screened an shRNA library targeting all genes deleted in prostate cancer (the prostate cancer deletome: 4380 shRNAs targeting 730 genes) for next generation antiandrogen resistance using a clinically-validated model of enzalutamide-sensitive, AR-driven mCRPC LNCaP/AR. The Chromatin helicase DNA-binding factor (CHD1) scored as a top candidate and was validated in vitro and in vivo using multiple independent shRNAs and CRISPR guides. Mechanistically, CHD1 loss led to global changes in open and closed chromatin (ATAC-seq) as well as downregulation of canonical AR target genes upon the challenge of antiandrogen, despite robust AR expression. Integrative analysis of ATAC- and RNA-seq changes following CHD1 deletion identified 23 candidate transcription factor drivers of enzalutamide resistance. CRISPR-based unbiased functional screening identified 4 of these drivers may drive the AR-independent resistance, including glucocorticoid receptor (GR), BRN2, NR2F1 and TBX2. Genetic studies further establish that CHD1 loss confers antiandrogen resistance by converting mCRPC cells from AR-dependence to GR-dependence in one of the resistant LNCaP/AR clone. Thus, CHD1 functions as a molecular tuner to regulate chromatin plasticity and maintain oncogenic AR signaling, as well as AR dependency.
2020-03-26 | GSE126917 | GEO
Project description:Next generation androgen receptor (AR) signaling inhibitors have significantly improved the survival of men with metastatic castration-resistant prostate cancer (mCPRC) but resistance remains a problem. Genomic alterations at the AR locus are present in ~50% of mCRPC patients, typically in association with large numbers of copy number gains and losses across the genome. To explore the functional consequences of these copy number alterations, we screened an shRNA library targeting all genes deleted in prostate cancer (the prostate cancer deletome: 4380 shRNAs targeting 730 genes) for next generation antiandrogen resistance using a clinically-validated model of enzalutamide-sensitive, AR-driven mCRPC LNCaP/AR. The Chromatin helicase DNA-binding factor (CHD1) scored as a top candidate and was validated in vitro and in vivo using multiple independent shRNAs and CRISPR guides. Mechanistically, CHD1 loss led to global changes in open and closed chromatin (ATAC-seq) as well as downregulation of canonical AR target genes upon the challenge of antiandrogen, despite robust AR expression. Integrative analysis of ATAC- and RNA-seq changes following CHD1 deletion identified 23 candidate transcription factor drivers of enzalutamide resistance. CRISPR-based unbiased functional screening identified 4 of these drivers may drive the AR-independent resistance, including glucocorticoid receptor (GR), BRN2, NR2F1 and TBX2. Genetic studies further establish that CHD1 loss confers antiandrogen resistance by converting mCRPC cells from AR-dependence to GR-dependence in one of the resistant LNCaP/AR clone. Thus, CHD1 functions as a molecular tuner to regulate chromatin plasticity and maintain oncogenic AR signaling, as well as AR dependency.
2020-03-26 | GSE127957 | GEO
Project description:Next generation androgen receptor (AR) signaling inhibitors have significantly improved the survival of men with metastatic castration-resistant prostate cancer (mCPRC) but resistance remains a problem. Genomic alterations at the AR locus are present in ~50% of mCRPC patients, typically in association with large numbers of copy number gains and losses across the genome. To explore the functional consequences of these copy number alterations, we screened an shRNA library targeting all genes deleted in prostate cancer (the prostate cancer deletome: 4380 shRNAs targeting 730 genes) for next generation antiandrogen resistance using a clinically-validated model of enzalutamide-sensitive, AR-driven mCRPC LNCaP/AR. The Chromatin helicase DNA-binding factor (CHD1) scored as a top candidate and was validated in vitro and in vivo using multiple independent shRNAs and CRISPR guides. Mechanistically, CHD1 loss led to global changes in open and closed chromatin (ATAC-seq) as well as downregulation of canonical AR target genes upon the challenge of antiandrogen, despite robust AR expression. Integrative analysis of ATAC- and RNA-seq changes following CHD1 deletion identified 23 candidate transcription factor drivers of enzalutamide resistance. CRISPR-based unbiased functional screening identified 4 of these drivers may drive the AR-independent resistance, including glucocorticoid receptor (GR), BRN2, NR2F1 and TBX2. Genetic studies further establish that CHD1 loss confers antiandrogen resistance by converting mCRPC cells from AR-dependence to GR-dependence in one of the resistant LNCaP/AR clone. Thus, CHD1 functions as a molecular tuner to regulate chromatin plasticity and maintain oncogenic AR signaling, as well as AR dependency.
2020-03-26 | GSE127241 | GEO
Project description:Gene expression profiling of LNCaP prostate cancer cells that have JMJD2A knockdown (JMJD2A shRNA #3; JMJD2A shRNA #5) or ETV knockdown (ETV shRNA #1; ETC shRNA #5) were compared to non-targeted control (sh-cm) cells. Total RNA was isolated from transformed LNCaP human prostate cancer cells containing a non-trageting control vector (sh-cm), vectors containing shRNA sequences for JMJD2A or ETV1 genes.
2014-01-01 | E-GEOD-47750 | biostudies-arrayexpress
Project description:Purpose: The goal of this study is to identify transcriptome-wide changes that occur in a human prostate cell line with knockdown of MAP3K7(TAK1) and CHD1, in the presence and absence of androgens. We utilize this cell line as a model of an aggressive prostate cancer subtype consisting of deletions of both MAP3K7 and CHD1 in human patients. RNAseq comparing shControl and shMAP3K7/shCHD1 was used to identify transcriptome changes resulting from loss of these genes, as well as their effects on androgen signaling. Abstract of associated study: Prostate cancer (PCa) genomic subtypes that stratify aggressive disease and inform treatment decisions at the primary stage are currently limited. Previously, we functionally validated an aggressive subtype present in 15% of PCa characterized by dual deletion of MAP3K7 and CHD1. Recent studies in the field have focused on deletion of CHD1 and its role in androgen receptor (AR) chromatin distribution and resistance to AR-targeted therapy, however, CHD1 is rarely lost without co-deletion of MAP3K7. Here we show that in the clinically relevant context of co-loss of MAP3K7 and CHD1 there are significant, collective changes to aspects of AR signaling. While CHD1 loss mainly impacts the expansion of the AR cistrome, loss of MAP3K7 drives increased AR target gene expression. PCa cell line models engineered to co-suppress MAP3K7 and CHD1 also demonstrated increased AR-v7 expression and resistance to the AR-targeting drug enzalutamide. Furthermore, we determined that low protein expression of both genes is significantly associated with biochemical recurrence (BCR) in a clinical cohort of radical prostatectomy specimens. Low MAP3K7 expression, however, was the strongest independent predictor for risk of BCR over all other tested clinicopathologic factors including CHD1 expression. Collectively, these findings illustrate the importance of MAP3K7 loss in a molecular subtype of PCa that poses challenges to conventional therapeutic approaches.
2021-04-12 | GSE168670 | GEO
Project description:Purpose: The goal of this study is to identify transcriptome-wide changes that occur in a human prostate cell line with knockdown of MAP3K7(TAK1) and CHD1, in the presence and absence of androgens. We utilize this cell line as a model of an aggressive prostate cancer subtype consisting of deletions of both MAP3K7 and CHD1 in human patients. RNAseq comparing shControl and shMAP3K7/shCHD1 was used to identify transcriptome changes resulting from loss of these genes, as well as their effects on androgen signaling. Abstract of associated study: Prostate cancer (PCa) genomic subtypes that stratify aggressive disease and inform treatment decisions at the primary stage are currently limited. Previously, we functionally validated an aggressive subtype present in 15% of PCa characterized by dual deletion of MAP3K7 and CHD1. Recent studies in the field have focused on deletion of CHD1 and its role in androgen receptor (AR) chromatin distribution and resistance to AR-targeted therapy, however, CHD1 is rarely lost without co-deletion of MAP3K7. Here we show that in the clinically relevant context of co-loss of MAP3K7 and CHD1 there are significant, collective changes to aspects of AR signaling. While CHD1 loss mainly impacts the expansion of the AR cistrome, loss of MAP3K7 drives increased AR target gene expression. PCa cell line models engineered to co-suppress MAP3K7 and CHD1 also demonstrated increased AR-v7 expression and resistance to the AR-targeting drug enzalutamide. Furthermore, we determined that low protein expression of both genes is significantly associated with biochemical recurrence (BCR) in a clinical cohort of radical prostatectomy specimens. Low MAP3K7 expression, however, was the strongest independent predictor for risk of BCR over all other tested clinicopathologic factors including CHD1 expression. Collectively, these findings illustrate the importance of MAP3K7 loss in a molecular subtype of PCa that poses challenges to conventional therapeutic approaches.
2021-04-12 | GSE168665 | GEO
Project description:Purpose: The goal of this study is to identify transcriptome-wide changes that occur in a human prostate cell line with knockdown of MAP3K7(TAK1) and CHD1, in the presence and absence of androgens. We utilize this cell line as a model of an aggressive prostate cancer subtype consisting of deletions of both MAP3K7 and CHD1 in human patients. RNAseq comparing shControl, shMAP3K7(TAK1), shCHD1, and both (shMAP3K7/shCHD1) was used to identify transcriptome changes resulting from loss of each of these genes, as well as their effects on androgen signaling. Abstract of associated study: Prostate cancer (PCa) genomic subtypes that stratify aggressive disease and inform treatment decisions at the primary stage are currently limited. Previously, we functionally validated an aggressive subtype present in 15% of PCa characterized by dual deletion of MAP3K7 and CHD1. Recent studies in the field have focused on deletion of CHD1 and its role in androgen receptor (AR) chromatin distribution and resistance to AR-targeted therapy, however, CHD1 is rarely lost without co-deletion of MAP3K7. Here we show that in the clinically relevant context of co-loss of MAP3K7 and CHD1 there are significant, collective changes to aspects of AR signaling. While CHD1 loss mainly impacts the expansion of the AR cistrome, loss of MAP3K7 drives increased AR target gene expression. PCa cell line models engineered to co-suppress MAP3K7 and CHD1 also demonstrated increased AR-v7 expression and resistance to the AR-targeting drug enzalutamide. Furthermore, we determined that low protein expression of both genes is significantly associated with biochemical recurrence (BCR) in a clinical cohort of radical prostatectomy specimens. Low MAP3K7 expression, however, was the strongest independent predictor for risk of BCR over all other tested clinicopathologic factors including CHD1 expression. Collectively, these findings illustrate the importance of MAP3K7 loss in a molecular subtype of PCa that poses challenges to conventional therapeutic approaches.
2021-04-12 | GSE168663 | GEO
Project description:Gene expression profiling of LNCaP prostate cancer cells that have JMJD2A knockdown (JMJD2A shRNA #3; JMJD2A shRNA #5) or ETV knockdown (ETV shRNA #1; ETC shRNA #5) were compared to non-targeted control (sh-cm) cells.
2014-01-01 | GSE47750 | GEO