Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA377752 | ENA |
REPOSITORIES: ENA
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Project description:CARM1-expressing ovarian cancer depends on the histone methyltransferase EZH2 activity
| PRJNA377750 | ENA
Project description:CARM1-expressing ovarian cancer depends on the histone methyltransferase EZH2 activity [ChIP-Seq]
| PRJNA377753 | ENA
Project description:CARM1 is an arginine methyltransferase that asymmetrically dimethylates protein substrates on arginine residues. CARM1 is often overexpressed in cancers and stimulates growth. However, clinically applicable therapeutic strategies based on CARM1 expression in cancer remains to be explored. Here we show that epithelial ovarian cancer is among the cancers with the highest CARM1 amplification rates that predicates a shorter survival. Our unbiased screen show that CARM1-expressing ovarian cancer cells are selectively sensitive to the inhibition of EZH2, another epigenetic regulator that silences its target genes. Inhibition of EZH2 activity using a clinically applicable small molecule inhibitor significantly suppressed the growth of CARM1-expressing ovarian tumors in two xenograft models. The observed selectivity correlates with upregulation of EZH2 target genes in a CARM1-dependent manner. CARM1 promotes EZH2 dependent gene silencing by methylating BAF155 to alter the antagonism between EZH2 and BAF155. Together, these results indicate that pharmacological inhibition of EZH2 is a novel therapeutic strategy for CARM1-expressing cancers.
2018-03-02 | GSE95644 | GEO
Project description:CARM1 is an arginine methyltransferase that asymmetrically dimethylates protein substrates on arginine residues. CARM1 is often overexpressed in cancers and stimulates growth. However, clinically applicable therapeutic strategies based on CARM1 expression in cancer remains to be explored. Here we show that epithelial ovarian cancer is among the cancers with the highest CARM1 amplification rates that predicates a shorter survival. Our unbiased screen show that CARM1-expressing ovarian cancer cells are selectively sensitive to the inhibition of EZH2, another epigenetic regulator that silences its target genes. Inhibition of EZH2 activity using a clinically applicable small molecule inhibitor significantly suppressed the growth of CARM1-expressing ovarian tumors in two xenograft models. The observed selectivity correlates with upregulation of EZH2 target genes in a CARM1-dependent manner. CARM1 promotes EZH2 dependent gene silencing by methylating BAF155 to alter the antagonism between EZH2 and BAF155. Together, these results indicate that pharmacological inhibition of EZH2 is a novel therapeutic strategy for CARM1-expressing cancers.
2018-03-02 | GSE95643 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE41651: Characterization of the EZH2-MMSET histone methyltransferase regulatory axis in cancer [expression] GSE41652: Characterization of the EZH2-MMSET histone methyltransferase regulatory axis in cancer [ChIP-seq] Refer to individual Series
2012-11-15 | E-GEOD-41653 | biostudies-arrayexpress
Project description:Schistosomiasis is a chronic and debilitating disease caused by a trematode of the genus Schistosoma. The current strategy for the control of the disease involves treatment with Praziquantel, the only available drug. The development of new drugs is therefore a top priority. Drugs that inhibit histone modifying enzymes have been used in cancer, altering gene expression, replication, repair and DNA recombination. Schistosoma parasites have some characteristics similar to malignant tumors, such as intense cell division and high levels of metabolic activity. Here we evaluate in Schistosoma mansoni the effect of GSK343, an inhibitor of the histone methyltransferase EZH2 that had been shown to arrest or reduce the growth of human cancer cells. We show that GSK343 causes damage to the parasite tegument and reduces egg laying in vitro, concomitant with a decrease in levels of H3K27me3, the histone mark put in place by EZH2. RNA-seq and proteomic analyses of treated parasites showed changes in the expression of hundreds of genes involved in important metabolic processes. In females, a marked decrease was observed in the expression of genes related to processes such as DNA replication and noncoding RNA metabolism. In conclusion, the histone methyltransferase EZH2 seems to be a promising novel drug target against schistosomiasis.
2018-11-23 | PXD010342 | Pride
Project description:The goal of this study is to identify ERalpha-target genes affected by overexpression of the histone arginine methyltransferase CARM1 in breast cancer cells. The roles of CARM1 in ERalpha+ breast cancer was not well characterized. Therefore, we created a Dox inducible CARM1 overexpressing MCF7 cell line where CARM1 is overexpressed by 2 fold to determine the created a Dox-inducible CARM1 overexpressing MCF7 cells for evaluation of the global effects of CARM1 on Eralpha-target gene expression. MCF7-tet-on-CARM1 clone 13 were treated under 4 conditions: DMSO; Dox; E2 (10nM); Dox+E2. In Dox+E2 condition, cells were pre-treated with Dox for 5 days before treating with E2 for 4 hours. 3 biological replicates were included and total of 12 samples were analyzed.
2011-06-01 | E-GEOD-26454 | biostudies-arrayexpress
Project description:Cancer cells exploit adaptive responses such as endoplasmic reticulum (ER) stress to support their survival. ER stress response is mediated in part by the ER-localized transmembrane sensor IRE1α endoribonuclease and its substrate XBP1 to regulate XBP1 target gene expression. However, the mechanism that controls the IRE1α/XBP1 pathway remains poorly understood. CARM1 is an oncogene that is often overexpressed in a number of cancer types including ovarian cancer. Here we report that CARM1 determines ER stress response by controlling the IRE1α/XBP1 pathway. Genome-wide profiling revealed that CARM1 regulates XBP1 target gene expression during ER stress response. CARM1 directly interacts with XBP1. Inhibition of the IRE1α/XBP1 pathway was effective in ovarian cancer in a CARM1-dependent manner both in vitro and in vivo in orthotopic and patient-derived xenograft models. In addition, IRE1α inhibitor B-I09 synergizes with immune checkpoint blockade anti-PD1 antibody in an immunocompetent CARM1-expressing ovarian cancer model.
2021-08-11 | GSE157116 | GEO
Project description:Cancer cells exploit adaptive responses such as endoplasmic reticulum (ER) stress to support their survival. ER stress response is mediated in part by the ER-localized transmembrane sensor IRE1α endoribonuclease and its substrate XBP1 to regulate XBP1 target gene expression. However, the mechanism that controls the IRE1α/XBP1 pathway remains poorly understood. CARM1 is an oncogene that is often overexpressed in a number of cancer types including ovarian cancer. Here we report that CARM1 determines ER stress response by controlling the IRE1α/XBP1 pathway. Genome-wide profiling revealed that CARM1 regulates XBP1 target gene expression during ER stress response. CARM1 directly interacts with XBP1. Inhibition of the IRE1α/XBP1 pathway was effective in ovarian cancer in a CARM1-dependent manner both in vitro and in vivo in orthotopic and patient-derived xenograft models. In addition, IRE1α inhibitor B-I09 synergizes with immune checkpoint blockade anti-PD1 antibody in an immunocompetent CARM1-expressing ovarian cancer model.
2021-08-11 | GSE157117 | GEO
Project description:The goal of this study is to identify ERalpha-target genes affected by overexpression of the histone arginine methyltransferase CARM1 in breast cancer cells. The roles of CARM1 in ERalpha+ breast cancer was not well characterized. Therefore, we created a Dox inducible CARM1 overexpressing MCF7 cell line where CARM1 is overexpressed by 2 fold to determine the created a Dox-inducible CARM1 overexpressing MCF7 cells for evaluation of the global effects of CARM1 on Eralpha-target gene expression.
2011-06-01 | GSE26454 | GEO