CHD1 Alters Sensitivity to Aurora Kinase A Inhibitors
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE186633 | GEO | 2023/10/16
REPOSITORIES: GEO
Similar Datasets
Project description:CHD1 Alters Sensitivity to Aurora Kinase A Inhibitors
| PRJNA774875 | ENA
Project description:Deregulation of chromatin architecture is emerging as a critical feature of carcinogenesis, and genomic alterations in nucleosome remodelers are common in human cancer. Recurrent deletion of the chromatin remodeler CHD1 is among the most common alterations in prostate cancer, but its role as a tumor suppressor and the reasons for the tissue-specific nature of CHD1 deletion remain undefined. Here, we show that deletion of CHD1 drives prostate tumorigenesis and fundamentally reprograms the transcriptional program of the androgen receptor (AR), diverting AR towards an oncogenic transcriptional program and away from a growth suppressive transcriptome. Conditional deletion of Chd1 in mouse prostate resulted in prostate neoplasia in vivo, confirming CHD1 as a tumor suppressor in prostate tissue. In prostate cells, the interactome of chromatin-bound CHD1 was enriched for factors that regulate nuclear receptor function, and interrogation of the CHD1 cistrome revealed promoter-independent enrichment of CHD1 at sites specifically occupied by AR and its associated transcriptional regulators. Deletion of CHD1 resulted in a dramatic redistribution of AR across the genome, localizing AR to sites enriched for HOXB13, and depleting AR at AR-halfsite motifs, consistent with the AR cistrome and epigenetic marks in human prostate cancer samples. Furthermore, the CHD1 null AR cistrome was associated with a unique AR transcriptional signature, enriched for pro-oncogenic pathways and depleted for processe consistent with normal prostatic function. Collectively, these data implicate CHD1 as a prostate-specific tumor suppressor which constrains the oncogenic functions of AR though maintenance of a normal AR transcriptional program.
2019-07-18 | GSE117429 | GEO
Project description:Sonic hedgehog medulloblastoma cells with stable overexpression of Myc (UW426-Myc) become sensitized to apoptosis induction when exposed to Aurora kinase B inhibitor AZD1152. We sought to determine the gene expression changes that take place when Myc is overexpressed in UW426 and to determine the genes differentially expressed in UW426-Myc cells compared to wild-type UW426 when exposed tothe drug AZD1152 that specifically inhibits Aurora kinase B activity.
2021-04-01 | GSE159385 | GEO
Project description:Deregulation of chromatin architecture is emerging as a critical feature of carcinogenesis, and genomic alterations in nucleosome remodelers are common in human cancer. Recurrent deletion of the chromatin remodeler CHD1 is among the most common alterations in prostate cancer, but its role as a tumor suppressor and the reasons for the tissue-specific nature of CHD1 deletion remain undefined. Here, we show that deletion of CHD1 drives prostate tumorigenesis and fundamentally reprograms the transcriptional program of the androgen receptor (AR), diverting AR towards an oncogenic transcriptional program and away from a growth suppressive transcriptome. Conditional deletion of Chd1 in mouse prostate resulted in prostate neoplasia in vivo, confirming CHD1 as a tumor suppressor in prostate tissue. In prostate cells, the interactome of chromatin-bound CHD1 was enriched for factors that regulate nuclear receptor function, and interrogation of the CHD1 cistrome revealed promoter-independent enrichment of CHD1 at sites specifically occupied by AR and its associated transcriptional regulators. Deletion of CHD1 resulted in a dramatic redistribution of AR across the genome, localizing AR to sites enriched for HOXB13, and depleting AR at AR-halfsite motifs, consistent with the AR cistrome and epigenetic marks in human prostate cancer samples. Furthermore, the CHD1 null AR cistrome was associated with a unique AR transcriptional signature, enriched for pro-oncogenic pathways and depleted for processes consistent with normal prostatic function. Collectively, these data implicate CHD1 as a prostate-specific tumor suppressor which constrains the oncogenic functions of AR though maintenance of a normal AR transcriptional program.
2019-07-18 | GSE123333 | GEO
Project description:Deregulation of chromatin architecture is emerging as a critical feature of carcinogenesis, and genomic alterations in nucleosome remodelers are common in human cancer. Recurrent deletion of the chromatin remodeler CHD1 is among the most common alterations in prostate cancer, but its role as a tumor suppressor and the reasons for the tissue-specific nature of CHD1 deletion remain undefined. Here, we show that deletion of CHD1 drives prostate tumorigenesis and fundamentally reprograms the transcriptional program of the androgen receptor (AR), diverting AR towards an oncogenic transcriptional program and away from a growth suppressive transcriptome. Conditional deletion of Chd1 in mouse prostate resulted in prostate neoplasia in vivo, confirming CHD1 as a tumor suppressor in prostate tissue. In prostate cells, the interactome of chromatin-bound CHD1 was enriched for factors that regulate nuclear receptor function, and interrogation of the CHD1 cistrome revealed promoter-independent enrichment of CHD1 at sites specifically occupied by AR and its associated transcriptional regulators. Deletion of CHD1 resulted in a dramatic redistribution of AR across the genome, localizing AR to sites enriched for HOXB13, and depleting AR at AR-halfsite motifs, consistent with the AR cistrome and epigenetic marks in human prostate cancer samples. Furthermore, the CHD1 null AR cistrome was associated with a unique AR transcriptional signature, enriched for pro-oncogenic pathways and depleted for processe consistent with normal prostatic function. Collectively, these data implicate CHD1 as a prostate-specific tumor suppressor which constrains the oncogenic functions of AR though maintenance of a normal AR transcriptional program.
2019-07-18 | GSE117430 | GEO
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:U-2 OS (human osteosarcoma cell line) were treated with ZM447439 (an aurora kinase inhibitor), SB202190 (a p38 inhibitor) or ZM447439+SB202190 and resulting changes in gene expression were profiled.
2017-07-01 | E-MTAB-1210 | biostudies-arrayexpress
Project description:Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Patients usually undergo surgery followed by aggressive radio- and chemotherapy with the alkylating agent temozolomide (TMZ). Still, median survival is only 12-15 months after diagnosis. Many human cancers including GBMs demonstrate addiction to MYC transcription factor signaling and can become susceptible to inhibition of MYC downstream genes. JQ1 is an effective inhibitor of BET Bromodomains, a class of epigenetic readers regulating expression of downstream MYC targets. Here, we show that BET inhibition decreases viability of patient-derived GBM cell lines. We propose a distinct expression signature of MYCN-elevated GBM cells that correlates with significant sensitivity to BET inhibition. In tumors showing JQ1 sensitivity, we found enrichment of pathways regulating cell cycle, DNA damage response and repair. As DNA repair leads to acquired chemoresistance to TMZ, JQ1 treatment in combination with TMZ synergistically inhibited proliferation of sensitive cells. Bioinformatic analyses showed that JQ1-sensitive cells could also respond to Aurora Kinase A inhibition which indeed showed synergistic efficacy in combination with BET inhibition. Collectively, our data suggest that BET inhibition could potentiate the efficacy of TMZ or could be combined with Aurora Kinase inhibitors in MYCN-elevated GBM.
2019-12-05 | GSE138942 | GEO
Project description:To study the senescence gene signatures in the cells, which were genetic SMARCB1 depleted or treated with aurora kinase inhibitors or etoposide, we performed next generation RNA sequencing on these cell, and 'FRIDMAN_SENESCENCE_UP' geneset was used to determine the enrichment of senescence-related genes. The RNA sequencing results include (1) A375 cells and SMARCB1 depleted counterparts. (2) A549 cells and aurora kinase inhibitor (Alisertib, barasertib or tozasertib) or etoposide treated counterparts.
2017-09-21 | GSE102639 | GEO
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.
2011-12-19 | GSE33531 | GEO