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GSE62251
Homo sapiens
21 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Inhibition of the autocrine IL-6-JAK2-STAT3-calprotectin axis as targeted therapy for HR-/HER2+ breast cancers.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 21 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Gene expression profiling of ErbB2-engineered MCF10A and WT cells in 2D and 3D culture
Publication Title
Inhibition of the autocrine IL-6-JAK2-STAT3-calprotectin axis as targeted therapy for HR-/HER2+ breast cancers.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
IlluminaHiSeq2500
Description
This study was aimed at understanding the genome-wide binding and regulatory role of the DAXX transcriptional repressor, recently implicated in PCa. ChIP-Seq analysis of genome-wide distribution of DAXX in PC3 cells revealed over 59,000 DAXX binding sites, found at regulatory enhancers and promoters. ChIP-Seq analysis of DNA methyltransferase 1 (DNMT1), which is a key epigenetic partner for DAXX repression, revealed that DNMT1 binding was restricted to a small number of DAXX sites. DNMT1 and DAXX bound close to transcriptional activator motifs. DNMT1 sites were found to be dependent on DAXX for recruitment by analyzing DNMT1 ChIP-Seq following DAXX knockdown (K/D), corroborating previous findings that DAXX recruits DNMT1 to repress its target genes. Massively parallel RNA sequencing (RNA-Seq) was used to compare the transcriptomes of WT and DAXX K/D PC3 cells. Genes induced by DAXX K/D included those involved in autophagy, and DAXX ChIP-Seq peaks were found close to the transcription start sites (TSS) of autophagy genes, implying they are more likely to be regulated by DAXX. Overall design: Determine changes in gene expression levels between WT and DAXX K/D prostate cancer cells by RNA-Seq (PC3 Cells).
Publication Title
The DAXX co-repressor is directly recruited to active regulatory elements genome-wide to regulate autophagy programs in a model of human prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Estrogen signaling and epigenetic modifications, in particular DNA methylation, are involved in regulation of gene expression in breast cancers. Here we investigated a potential regulatory cross-talk between these two pathways by identifying their common target genes and exploring potential underlying molecular mechanisms in human MCF7 breast cancer cells. Principal Findings: Gene expression profiling revealed that the expression of approximately 150 genes was influenced by both 17-estradiol (E2) and a hypomethylating agent 5-aza-2-deoxycytidine (DAC). Based on gene ontology (GO), CpG island prediction analysis and previously reported estrogen receptor (ER) binding regions, we selected six genes for further analysis (BTG3, FHL2, PMAIP1, BTG2, CDKN1A and TGFB2). GO analysis suggests that these genes are involved in intracellular signaling cascades, regulation of cell proliferation and apoptosis, while CpG island prediction of promoter regions reveals that the promoters of these genes contain at least one CpG island. Using chromatin immunoprecipitation, we show that ER is recruited to CpG islands in promoters, but neither in an E2- nor in a DAC-dependent fashion. DAC treatment reactivates the expression of all selected genes although only the promoters of BTG3 and FHL2 genes are methylated, with E2 treatment showing no effect on the methylation status of these promoters. Conclusions: We identified a set of genes regulated by both estrogen signaling and DNA methylation. However, our data does not support a direct molecular interplay of mediators of estrogen and epigenetic signaling at promoters of regulated genes.
Publication Title
Global identification of genes regulated by estrogen signaling and demethylation in MCF-7 breast cancer cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In order to confirm the role of fatty acid -oxidation in Src regulation, we performed gene expression analysis in MDA231 cells from in vivo model treated with ETX or knockdown of CPT1 or CPT2 using shRNA. As expected, inhibition of -oxidation showed a gene expression pattern that is opposite to the published Src regulated gene pattern. The known Src up-regulated genes are down-regulated and Src down-regulated genes are up-regulated in -oxidation inhibited cells. Western Blotting further confirmed the gene expression pattern. Knockdown of CPT1 or CPT2 inhibited Src Y416 autophosphorylation as observed with ETX.
Publication Title
Fatty Acid Oxidation-Driven Src Links Mitochondrial Energy Reprogramming and Oncogenic Properties in Triple-Negative Breast Cancer.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used a transmitochondrial cybrid (cybrids)-based discovery approach to identify mitochondria-regulated cancer pathways in TN BCa. Cybrids were generated under a moderately metastatic TN BCa cell line SUM159 as the common nuclear background with mitochondria from benign breast epithelium (A1N4) and moderately metastatic (SUM159) TN BCa cells. In vitro and in vivo studies suggested that even under the common moderately cancerous nuclear background, mitochondria from benign cells inhibit and metastatic cell induce cancer properties of a moderately aggressive TN BCa cell. Gene expression studies identified c-Src onco-pathway as one of the major cancer pathways altered according to the mitochondria status of the cybrids.
Publication Title
Fatty Acid Oxidation-Driven Src Links Mitochondrial Energy Reprogramming and Oncogenic Properties in Triple-Negative Breast Cancer.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 26 Downloadable Samples
- Illumina HiSeq 2500
Description
The Nanos family of RNA-binding proteins has been implicated in the specification of primordial germ cells (PGCs) in a wide range of metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of PGCs lacking the nanos homologues nos-1 and nos-2 in C. elegans using cell sorting and RNA-seq. nos-1nos-2 PGCs fail to silence hundreds of genes normally expressed in oocytes and somatic cells, a phenotype reminiscent of PGCs lacking the repressive PRC2 complex. The nos-1nos-2 phenotype depends on LIN-15B, a broadly expressed synMuvB class transcription factor known to antagonize PRC2 activity in somatic cells. LIN-15B is maternally-inherited by all embryonic cells and is down-regulated specifically in PGCs in a nos-1nos-2-dependent manner. Consistent with LIN-15B being a critical target of Nanos regulation, inactivation of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These studies demonstrate a central role for Nanos in reprogramming the transcriptome of primordial germ cells away from an oocyte/somatic fate by down-regulating an antagonist of PRC2 activity. Overall design: 30 RNA-seq samples are inclued in this study. These include PGC transcriptomes from wild-type, nos-1(gv5)nos-2(RNAi), mes-2(RNAi), mes-4(RNAi), nos-1(gv5)nos-2(RNAi);lin15-B(RNAi) and biological replicates.
Publication Title
Recruitment of mRNAs to P granules by condensation with intrinsically-disordered proteins.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Exposure to ultraviolet (UV) irradiation is the major cause of nonmelanoma skin cancer, the most common form of cancer in the United States. UV irradiation has a variety of effects on the skin associated with carcinogenesis, including DNA damage and effects on signal transduction. The alterations in signaling caused by UV regulate inflammation, cell proliferation, and apoptosis. UV also activates the orphan receptor tyrosine kinase and proto-oncogene Erbb2 (HER2/neu). In this study, we demonstrate that the UV-induced activation of Erbb2 regulates the response of the skin to UV. Inhibition or knockdown of Erbb2 before UV irradiation suppressed cell proliferation, cell survival, and inflammation after UV. In addition, Erbb2 was necessary for the UV-induced expression of numerous proinflammatory genes that are regulated by the transcription factors nuclear factor-kappaB and Comp1, including interleukin-1beta, prostaglandin-endoperoxidase synthase 2 (Cyclooxygenase-2), and multiple chemokines. These results reveal the influence of Erbb2 on the UV response and suggest a role for Erbb2 in UV-induced pathologies such as skin cancer.
Publication Title
Erbb2 regulates inflammation and proliferation in the skin after ultraviolet irradiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Impact of human MLL/COMPASS and polycomb complexes on the DNA methylome.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The association of DNA CpG methylation (or its absence) with occupancy of histone post translational modifications has hinted at an underlying crosstalk between histone marks and DNA methylation in patterning the human methylome, an idea supported by corresponding alterations to both histone marks and DNA methylation during malignant transformation. This study investigated the framework by which histone marks influence DNA methylation. Using RNAi in a human pluripotent embryonic carcinoma cell line we depleted essential components of the histone modifying complexes that establish the posttranslational modifications H3K4me3, H3K27me3, and H2AK119ub, and we assayed the impact of the subsequent loss of these marks on the DNA methylome. Absence of H2AK119ub resulted predominantly in hypomethylation across the genome. Removal of H3K4me3 or, surprisingly, H3K27me3 caused CpG island hypermethylation at a subset of loci. Intriguingly, many promoters were co-regulated by all three histone marks, becoming hypermethylated with loss of H3K4me3 or H3K27me3 and becoming hypomethylated with depletion of H2AK119ub, and many of these co-regulated loci were among those that are commonly, aberrantly hypermethylated in cancer.
Publication Title
Impact of human MLL/COMPASS and polycomb complexes on the DNA methylome.
Sample Metadata Fields
Specimen part, Cell line
View Samples