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Use the form below to search 9,145 publicly available datasets published in the Gene Expression Omnibus database and processed by ARCHS4.

 
Transcriptome profiles of POM121-knockout prostate cancer cell lines
GSE103637
22 samples
Published August 2018
Summary
Nucleoporins are major constituents of nuclear pore complexes, molecular conglomerates embedded within the nuclear envelope that participate in bidirectional trafficking between nucleus and cytoplasm, chromatin silencing and organization, and transcriptional regulation . This functional vantage point is of utmost importance for fundamental cell processes such as intracellular signaling, cell migration, DNA repair and cell division, all of which can be impaired when the molecular identity of the NE and nuclear pore complex is compromised, as seen in cancer. Here we identify a nucleoporin POM121 as a key regulator of proliferation, tumourigenesis, and survival in chemoresistant prostate cancer. Mechanistically, POM121 regulates nuclear transport of specific survival-conferring transcription factors (MYC and E2F1) and androgen receptor that have been previously linked with advanced stages of prostate cancer. POM121-mediated deregulation of nucleocytoplasmic transport occurs through its interaction with Importin β, which serves as a pharmacological target that decreases tumour growth, sensitizes the tumor cells to standard chemotherapy, and improves survival of patient-derived xenograft mice. These results indicate that nuclear pore complex represents a novel mechanism of chemoresistance, which can be therapeutically targetable in aggressive prostate cancer.
Organism
Homo sapiens
A novel transcriptional network for the Androgen Receptor in human epididymis epithelial cells [RNA-Seq]
GSE109062
8 samples
Published August 2018
Summary
The androgen receptor (AR) has a pivotal role in regulating gene expression in the male reproductive system. Due to the involvement of AR in prostate cancer, its role is best studied in the prostate gland epithelium and prostate cancer cell lines. Here we investigate the transcriptional program of AR in normal human epididymis epithelial (HEE) cells. After AR stimulation of caput HEE cells with the synthetic androgen R1881, AR targets were revealed with RNA-sequencing. Next, AR occupancy genome-wide was determined in control or R1881-stimulated HEE cells by chromatin immunoprecipitation and deep sequencing (ChIP-seq). The results identify about 200 genes that are differentially expressed (DEGs) in HEE cells after AR activation. Some of these DEGs show occupancy of AR at their promoters or cis-regulatory elements suggesting direct regulation. However there is little overlap in AR-associated DEGs between HEE and prostate epithelial cells. Inspection of over-represented motifs in AR ChIP-seq peaks identified CAAT-enhancer binding protein beta (CEBPB) and Runt-related transcription factor 1 (RUNX1) as potential co-factors, with no evidence for FOXA1, which is an important co-factor in the prostate epithelium. CEBPB and RUNX1 ChIP-seq in HEE cells showed that both these factors often occupied AR-binding sites, though rarely simultaneously. Further analysis at a single AR-regulated locus (FK506-binding protein 5, FKPB5) suggests that RUNX1 may inhibit AR occupancy, while CEBP appears to be a co-activator. These data suggest a novel AR transcriptional network governs differentiated functions of the human epididymis epithelium.
Organism
Homo sapiens
Robust prediction of response to immune checkpoint blockade therapy in metastatic melanoma
GSE115821
7 samples
Published August 2018
Summary
Immune checkpoint blockade (ICB) therapy provides remarkable clinical gains, where melanoma is at the forefront of its success. However, only a subset of patients with advanced tumors currently benefit from these therapies, which at times incur considerable side-effects and costs. Constructing such predictors of patient’s response has remained a serious challenge due to the complexity of the immune response and the shortage of large ICB-treated patient cohorts including both omics and response data. Here we build IMPRES, a predictor of ICB-response in melanoma which encompasses 15 pairwise transcriptomics relations between immune checkpoint genes. It is based on two key conjectures: (a) immune mechanisms underlining spontaneous regression in neuroblastoma can predict ICB response in melanoma, and (b) key immune interactions can be captured via specific pairwise relations of immune checkpoint genes’ expression. IMPRES is validated on 9 published datasets1–6 and on a newly generated dataset of 31 tumor samples treated with anti-PD-1 and 10 tumor samples treated with anti-CTLA-4 (some of these are treated with both antibodies), spanning 297 samples in total. It achieves an overall accuracy of AUC=0.83, outperforming existing predictors, capturing almost all true responders while misclassifying less than half of the non-responders. Future studies are warranted to determine the value of the approach presented here in other cancer types.
Organism
Homo sapiens
ARID2 promotes clear cell renal cell carcinoma in the absence of functional PBRM1 [RNA-seq]
GSE102806
10 samples
Published August 2018
Summary
Subunits of SWI/SNF chromatin remodeling complexes are frequently mutated in human malignancies. The PBAF complex is composed of multiple subunits, including the putative tumor suppressor proteins PBRM1 (BAF180) and ARID2 (BAF200) that are unique to this SWI/SNF complex. PBRM1 is mutated in various cancers, with a high mutation frequency in clear cell renal cell carcinoma (ccRCC). Here, we integrate RNA-seq, ARID2 and histone mark ChIP-seq, and ATAC-seq data to show that PBAF acts to enhance or repress gene expression depending on the genomic context. At baseline, ARID2 binds to areas of open chromatin at both active enhancers and promoters. Depletion of PBRM1 leads to attenuated and redistributed ARID2 chromatin binding that correlates significantly with gene expression changes. At enhancers, ARID2 binding loss leads to diminishment of the histone mark H3K4me1 and gene downregulation. Alternatively, at a subset of promoters, ARID2 binding loss derepresses gene expression. Interestingly, ARID2, which remains bound to other PBAF subunits after loss of PBRM1, is essential for many of the pro-tumorigenic transcriptional changes observed after loss of PBRM1, whereas other core SWI/SNF components are dispensable. Upon loss of PBRM1, ARID2 positively regulates cancer-related genes and pathways, including the cancer stem cell marker ALDH1A1 and ­­­EG­F signaling, to stimulate tumor cell growth. Therefore, ARID2 is crucial for maintaining the transformed state of PBRM1-deficient ccRCC cells. In total, this study suggests a novel mechanism of transcriptional control by PBRM1, whereby its loss alters the chromatin distribution of the residual PBAF complex leading to altered transcription that promotes tumorigenesis.
Organism
Homo sapiens
Therapeutic efficacy of BET bromodomain protein inhhibitor and PD-1 blockade in genetically engineered mouse model of non-small cell lung cancer
GSE114601
8 samples
Published August 2018
Summary
KRAS mutation is present in about 30% of human lung adenocarcinomas. While recent advances in targeted therapy have shown great promise, KRAS remains undruggable and concurrent alterations in tumor suppressors render KRAS mutant tumors even more resistant to existing therapies. Contributing to the refractoriness of KRAS mutant tumors harboring these co-mutations are immunosuppressive mechanisms such as increased presence of suppressive Tregs in tumors and elevated expression of the inhibitory receptor PD-1 on tumor-infiltrating T cells. BET bromodomain inhibitors demonstrate clinical benefit in hematologic malignancies, and prior reports demonstrate their Treg-disruptive effects in a NSCLC model. Targeting PD-1 inhibitory signals through anti-PD-1 antibody blockade has also shown substantial therapeutic impact in lung cancer although these outcomes are still limited to a minor pool of patients. We therefore hypothesized that the BET bromodomain inhibitor JQ1 would synergize with PD-1 blockade to promote robust anti-tumor response in lung cancer. In the present study, using Kras+/LSL-G12D; Trp53L/L (KP) mouse models of non-small cell lung cancer, we identified cooperative effects between JQ1 and anti-PD-1 antibody that included reduced numbers of tumor-infiltrating Tregs and enhanced activation of tumor-infiltrating T cells, which exhibited a Th1 cytokine profile that favored their demonstrated improved effector function. Furthermore, lung-tumor-bearing mice under this combinatorial treatment regimen showed robust and long-lasting anti-tumor responses compared to either agent alone, culminating in substantial improvement in the survival of treated mice. Thus, combining BET bromodomain inhibition with immune checkpoint blockade offers a promising therapeutic approach for solid malignancies such as lung adenocarcinoma.
Organism
Mus musculus
Cooperative Regulation of Normal and Neoplastic Hepatocyte Proliferation by Myc and ChREBP
GSE114634
37 samples
Published August 2018
Summary
By analogy to the c-Myc (Myc)/Max family of transcription factors, there also exists a “parallel” network of structurally and functionally related bHLH-ZIP proteins with certain Myc-like functions. Two closely related “Myc-like” paralogs termed Mondo A and MondoB/ChREBP (ChREBP) positively regulate gene expression in heterodimeric association with the Max-like factor Mlx. Myc is necessary to support liver cancer cell growth but not for normal hepatocyte proliferation. Here, we investigated the role for ChREBP and its relationship to Myc in these processes. Unlike Myc, ChREBP loss conferred a marked proliferative disadvantage to normal hepatocytes as did the loss of both ChREBP and Myc. In addition, hepatoblastomas (HBs) originating in myc-/-, chrebp-/- or myc-/-/chrebp-/- backgrounds grew significantly more slowly. Metabolic studies performed on livers and HBs arising in all three backgrounds showed marked differences in oxidative phosphorylation, fatty acid -oxidation (FAO) and the activity of pyruvate dehydrogenase. RNAseq of livers and HBs indicated seven distinct forms of target transcript regulation. Gene ontology analysis indicated that many transcripts de-regulated in the chrebp-/- background encode enzymes functioning in glycolysis, the TCA cycle and - and-FAO whereas those in myc-/- background encode enzymes for glycolysis, glutaminolysis and sterol biosynthesis. Transcript de-regulation in the double knockout group was similar but also included those involved in peroxisomal - and -FAO. Finally, we identified cooperative positive regulation by Myc and ChREBP of virtually all ribosomal protein genes. Our findings define the global proliferative, metabolic and transcriptional roles for the more general “Extended Myc Network” under both normal and neoplastic conditions.
Organism
Mus musculus
TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells [RNA-seq]
GSE107010
18 samples
Published August 2018
Summary
We report the gene expression profiles of TRPS-depleted and YAP 5SA overexpressing breast cancer cell lines.
Organism
Homo sapiens
TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer cells
GSE107023
18 samples
Published August 2018
Summary
This SuperSeries is composed of the SubSeries listed below.
Organism
Homo sapiens
Identification of relationships between Molecular and Imaging Phenotypes in Non-small cell lung cancer using radiogenomics Map
GSE103584
103 samples
Published August 2018
Summary
Purpose: To create a radiogenomic map linking computed tomographic (CT) image features and gene expression profiles generated by RNA sequencing for patients with non-small cell lung cancer (NSCLC). Methods: A cohort of 113 patients with NSCLC diagnosed between April 2008 and September 2014 who had preoperative CT data and tumor tissue available was studied. For each tumor, a thoracic radiologist recorded 87 semantic image features, selected to reflect radiologic characteristics of nodule shape, margin, texture, tumor environment, and overall lung characteristics. Next, total RNA was extracted from the tissue and analyzed with RNA sequencing technology. Ten highly coexpressed gene clusters, termed metagenes, were identified, validated in publicly available gene-expression cohorts, and correlated with prognosis. Next, a radiogenomics map was built that linked semantic image features to metagenes by using the t statistic and the Spearman correlation metric with multiple testing correction. Results: RNA sequencing analysis resulted in 10 metagenes that capture a variety of molecular pathways, including the epidermal growth factor (EGF) pathway. A radiogenomic map was created with 32 statistically significant correlations between semantic image features and metagenes. Conclusions: Radiogenomic analysis of NSCLC showed multiple associations between semantic image features and metagenes that represented canonical molecular pathways
Organism
Homo sapiens
Effect of CRISPR-Cas9 mediated knock-out of integrin alpha2 on the transcriptome of DU145 prostate cancer cell grown as a spheroid culture
GSE111507
9 samples
Published August 2018
Summary
CRISPR-cas9 technology was used to knock out alpha2 integrin in DU145 cells. To create two cell lines that could be compared to each other in an appropriate manner, these cells were transfected either with alpha2 integrin cDNA or empty vector. The objective of the study was to find potential alpha2 integrin regulated genes when the cells were grown as spheroids.
Organism
Homo sapiens