GEO DataSets

(Submitter supplied) xenograft, patientderived xenograft and the genetic Arid1aflox/flox/Pik3caH1047R mouse models. Finally, B-I09 synergizes with inhibition of HDAC6, a known regulator of the ER stress response, in suppressing the growth of ARID1A-inactivated OCCCs. These studies reveal a promising therapeutic strategy for ARID1A-mutant OCCCs and define the IRE1?-XBP1 axis of the ER stress response as a targetable vulnerability for ARID1A-mutant OCCCs. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

12 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

26 Samples

Download data: BW

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

8 Samples

Download data: BW

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

18 Samples

Download data: TXT

(Submitter supplied) ARID1A, encoding a subunit of the SWI/SNF chromatin remodeling complex, is the most mutated epigenetic regulator in human cancers. ARID1A and TP53 mutations are typically mutually exclusive. Therapeutic approaches that correlate with ARID1A mutational status remain a challenge. Here, we show that HDAC6 activity is essential in ARID1A-mutated ovarian cancers. Inhibition of HDAC6 activity using a clinically applicable small molecule inhibitor significantly improved the survival of mice bearing ARID1A-mutated ovarian tumors. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

5 Samples

Download data: TXT

(Submitter supplied) ARID1A, encoding a subunit of the SWI/SNF chromatin remodeling complex, is the most frequently mutated epigenetic regulators in human cancers. ARID1A is mutated in over 50% ovarian clear cell carcinoma, a disease currently has no effective therapy. Here we show that ARID1A-mutated ovarian cancer cells are selectively sensitive to inhibition of HDAC2 activity. HDAC2 interacts with EZH2 in an ARID1A status dependent manner. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

3 Samples

Download data: TXT

(Submitter supplied) ARID1A is frequently mutated in ovarian clear-cell carcinoma (OCCC) and often co-exists with activating mutations of PIK3CA. Although induction of pro-inflammatory cytokines has been observed in this cancer, the mechanism by which the two mutations synergistically activate cytokine genes remains elusive. Here we established an in vitro model of OCCC by introducing ARID1A knock-down and mutant PIK3CA in a normal human ovarian epithelial cell line, which resulted in cell transformation and cytokine gene induction. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

12 Samples

Download data: XLSX

(Submitter supplied) Tumors evade immune control by creating hostile microenvironments that perturb T cell metabolism and effector function. However, it remains unclear how intratumoral T cells integrate and interpret metabolic stress signals. Here we report that ovarian cancer (OvCa), an aggressive malignancy refractory to standard treatments and current immunotherapies, induces Endoplasmic Reticulum (ER) stress and activation of the IRE1α-XBP1 arm of the Unfolded Protein Response (UPR)10,11 in T cells to control their mitochondrial respiration and anti-tumor function. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

8 Samples

Download data: TXT

(Submitter supplied) IRE1a is a critical modulator of the unfolded protein response. Its RNAse activity generates the mature transcript for the XBP1 transcription factor and also degrades other ER associated mRNAs in a process termed Regulated IRE1a Dependent mRNA Decay or RIDD. To determine if IRE1a is critical in the response to oncogenic Ras we used ShRNA to knockdown Ire1a or Xbp1 in primary mouse epidermal keratinocytes transduced with a v-HRAS retrovirus.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL16570

12 Samples

Download data: CEL

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platform:

GPL18573

7 Samples

Download data: TXT

(Submitter supplied) The SWI/SNF chromatin remodeling complex is altered in ~20% of human cancers. ARID1A, a component of the SWI/SNF chromatin-remodeling complex, is the most frequently mutated epigenetic regulator in human cancers. Inactivation of the SWI/SNF complex is synthetically lethal with inhibition of EZH2 activity. EZH2 inhibitors are entering clinical trials for specific tumor types with SWI/SNF mutations. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

5 Samples

Download data: TXT

(Submitter supplied) The SWI/SNF chromatin remodeling complex is altered in ~20% of human cancers. ARID1A, a component of the SWI/SNF chromatin-remodeling complex, is the most frequently mutated epigenetic regulator in human cancers. Inactivation of the SWI/SNF complex is synthetically lethal with inhibition of EZH2 activity. EZH2 inhibitors are entering clinical trials for specific tumor types with SWI/SNF mutations. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

2 Samples

Download data: TXT

(Submitter supplied) Illumina array was employed to analyze the genes whose expression are altered when ARID1A gene is downregulated by shRNA in normal ovarian surface epithelial cells OSE4 and IOSE80pc. This leads to discovery of p53-regulated genes such as p21 and SMAD3.

Organism:

Homo sapiens

Type:

Expression profiling by array

Dataset:

GDS4826

Platform:

GPL10558

4 Samples

Download data: TXT

Analysis of OSE4 and IOSE80pc ovarian surface epithelial cells depleted for ARID1A, which encodes large nuclear protein p270. ARID1A depletion enhances OSE4 and IOSE80pc proliferation. OSE4 cells become highly tumorigenic upon ARID1A depletion. Results suggest a tumor-suppressor role for ARID1A.

Organism:

Homo sapiens

Type:

Expression profiling by array, transformed count, 2 cell line, 2 protocol sets

Platform:

GPL10558

Series:

GSE37684

4 Samples

Download data

(Submitter supplied) Purpose: microRNA profiles were generated from NIH-3T3 cells control and thapsigargin treated, in duplicate. The goal of this study was to compare microRNA profiles of untreated and thapsigargin treated NIH-3T3 fibroblast cells. Methods: NIH-3T3 cells were grown to confluency and either untreated or treated with 500 nM thapsigargin in media for 24 hours. Cells were harvested with TriZol and RNA isolated according to manufacturers protocol Analysis Outline: Short reads in fastq format were assembled using BclToFastq.pl script from Illumina CASAVA 1.8.1 software pipeline.Read quality was examined using FastQC program (http://www.bioinformatics.bbsrc.ac.uk/projects/fastqc). more...

Organism:

Mus musculus

Type:

Non-coding RNA profiling by high throughput sequencing

Platform:

GPL11002

4 Samples

Download data: TXT, XLSX

(Submitter supplied) Ovarian clear cell carcinoma (OCCC) is an aggressive form of ovarian cancer with high ARID1A mutation rates. Here we present a genetically engineered mouse model of OCCC. We find that ARID1A inactivation is not sufficient for tumor formation, but requires concurrent activation of the phosphoinositide 3-kinase catalytic subunit, PIK3CA. Remarkably, the mice develop highly penetrant tumors with OCCC-like histopathology, culminating in hemorrhagic ascites and a median survival period of 7.5 weeks. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL17400

18 Samples

Download data: CEL

(Submitter supplied) Natural killer (NK) cells are critical mediators of host immunity against infectious disease and cancer. The intrinsic regulators of NK cells are not fully understood. Here, we demonstrate that the ER stress sensor inositol-requiring enzyme 1 (IRE1α) and its substrate transcription factor X-box-binding protein 1 (XBP1) critically drive NK cell-mediated responses against viral infection and tumors. IRE1α and XBP1 were essential for the robust expansion of activated mouse and human NK cells. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

18 Samples

Download data: TXT

(Submitter supplied) The IRE1α-XBP1 arm of the unfolded protein response (UPR) maintains endoplasmic reticulum (ER) homeostasis, but also controls UPR-independent processes such as cytokine production and lipid metabolism. Yet, the physiological consequences of IRE1α-XBP1 activation in immune cells remain largely unexplored. Here, we report that leukocyte-intrinsic IRE1α-XBP1 signaling drives prostaglandin biosynthesis and pain. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

24 Samples

Download data: TXT

(Submitter supplied) IRE1a and XBP1 are key regulators of the unfolded protein response (UPR). XBP1 ablation causes profound hypolipidemia in mice, and triggers feedback activation of its upstream enzyme IRE1a, instigating regulated IRE1-dependent decay (RIDD), an mRNA degradation mechanism dependent on IRE1a's endoribonuclease activity. Comprehensive microarray analysis of XBP1 and/or IRE1a deficient liver identified genes involved in lipogenesis and lipoprotein metabolism as RIDD substrates, which might contribute to the suppression of plasma lipid levels by activated IRE1a.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL11180

31 Samples

Download data: CEL

(Submitter supplied) To gain insight into the global XBP1s target gene profile in prostate cancer cells, we performed RNA-seq analysis in LNCaP cells upon either XBP1 siRNA-mediated knockdown (siXBP1) or MKC8866-mediated IRE1α inhibition.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21290

16 Samples

Download data: TXT