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GSE72688
Homo sapiens
11 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Abnormal activities of histone lysine demethylases (KDMs) and lysine deacetylases (HDACs) are associated with aberrant gene expression in breast cancer development. However, the precise molecular mechanisms underlying the crosstalk between KDMs and HDACs in chromatin remodeling and regulation of gene transcription are still elusive. In this study, we showed that treatment of human breast cancer cells with inhibitors targeting the zinc cofactor dependent class I/II HDACs, but not NAD+ dependent class III HDACs, led to significant increase of H3K4me2 which is a specific substrate of histone lysine-specific demethylase 1 (LSD1) and a key chromatin mark promoting transcriptional activation. We also demonstrated that inhibition of LSD1 activity by a pharmacological inhibitor, pargyline, or siRNA resulted in increased acetylation of H3K9 (AcH3K9). However, siRNA knockdown of LSD2, a homolog of LSD1, failed to alter the level of AcH3K9, suggesting that LSD2 activity may not be functionally connected with HDAC activity. Combined treatment with LSD1 and HDAC inhibitors resulted in enhanced levels of H3K4me2 and AcH3K9, and exhibited synergistic growth inhibition of breast cancer cells. Finally, microarray screening identified a unique subset of genes whose expression was significantly changed by combination treatment with inhibitors of LSD1 and HDAC. Our study suggests that LSD1 intimately interacts with histone deacetylases in human breast cancer cells. Inhibition of histone demethylation and deacetylation exhibits cooperation and synergy in regulating gene expression and growth inhibition, and may represent a promising and novel approach for epigenetic therapy of breast cancer.
Publication Title
Inhibitors of histone demethylation and histone deacetylation cooperate in regulating gene expression and inhibiting growth in human breast cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We performed gene expression microarray to examine the potential effect that depletion of HDAC5 (an important HDAC isozyme) or LSD1 (an FAD-dependent histone lysine demethylase) has on the triple-negative breast cancer transcriptome.
Publication Title
HDAC5-LSD1 axis regulates antineoplastic effect of natural HDAC inhibitor sulforaphane in human breast cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Abnormal activities of histone lysine demethylases (KDMs) are associated with aberrant gene expression in breast cancer development. However, the precise molecular mechanisms in chromatin remodeling and regulation of gene transcription are still elusive. In this study, we performed Gene Expression Microarray (HG-U133A_2) using RNA from the aggressive breast cancer cell line MDA-MB-231 expressing stable knockdown or overexpression of LSD2. The goal of this study is to identify genes and pathways differentially expressed in triple negative breast cancer cells with genetically modified LSD2 expression.
Publication Title
No associated publication
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 419 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
With aging, significant changes in circadian rhythms occur, including a shift in phase toward a morning chronotype and a loss of rhythmicity in circulating hormones. However, the effects of aging on molecular rhythms in the human brain have remained elusive. Here we employed a previously-described time-of-death analyses to identify transcripts throughout the genome that have a significant circadian rhythm in expression in the human prefrontal cortex (Brodmanns areas (BA) 11 and 47). Expression levels were determined by microarray analysis in 146 individuals. Rhythmicity in expression was found in ~10% of detected transcripts (p<0.05). Using a meta-analysis across the two brain areas, we identified a core set of 235 genes (q<0.05) with significant circadian rhythms of expression. These 235 genes showed 92% concordance in the phase of expression between the two areas. In addition to the canonical core circadian genes, a number of other genes were found to exhibit rhythmic expression in the brain. Notably, we identified more than one thousand genes (1186 in BA11; 1591 in BA47) that exhibited age-dependent rhythmicity or alterations in rhythmicity patterns with aging. Interestingly, a set of transcripts gained rhythmicity in older individuals, which may represent a compensatory mechanism due to a loss of canonical clock function. Thus, we confirm that rhythmic gene expression can be reliably measured in human brain and identified for the first time significant changes in molecular rhythms with aging that may contribute to altered cognition, sleep and mood in later life.
Publication Title
Effects of aging on circadian patterns of gene expression in the human prefrontal cortex.
Sample Metadata Fields
Sex, Age, Specimen part, Race
View Samples- Homo sapiens
- 286 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Impairments in certain cognitive processes (e.g., working memory) are typically most pronounced in schizophrenia (SZ), intermediate in bipolar disorder (BP) and least in major depressive disorder (MDD).
Publication Title
Transcriptome Alterations in Prefrontal Pyramidal Cells Distinguish Schizophrenia From Bipolar and Major Depressive Disorders.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 207 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Schizophrenia is associated with alterations in working memory that reflect dysfunction of dorsolateral prefrontal cortex (DLPFC) circuitry. Working memory depends on the activity of excitatory pyramidal cells in DLPFC layer 3, and to a lesser extent in layer 5.
Publication Title
Distinctive transcriptome alterations of prefrontal pyramidal neurons in schizophrenia and schizoaffective disorder.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 141 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Schizophrenia is associated with dysfunction of the dorsolateral prefrontal cortex (DLPFC). This dysfunction is manifest as cognitive deficits that appear to arise from disturbances in gamma frequency oscillations.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 103 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Global gene expression patterns associated with early stage endometrial cancer have been reported, but changes in molecular expression associated with tumor grade, depth of myometrial invasion, and non-endometrioid histology have not been previously elucidated. Our group hypothesized there are unique genetic events underlying early endometrial carcinogenesis. Ninety-two samples of pathologically reviewed stage I endometrial cancers (80 endometrioid and 12 serous) with a heterogeneous distribution of grade and depth of myometrial invasion (i.e. 9 IAG1, 14 IAG2, 7 IAG3, 14 IBG1, 12 IBG2, 13 IBG3, 7 ICG1, 10 ICG2, and 6 ICG3) were examined in relation to 12 samples of atrophic endometrium from postmenopausal women. Specimens were analyzed using oligonucleotide microarray analysis and a subset of the differentially expressed transcripts was validated using quantitative PCR. Comparison of early stage cancers with normal endometrium samples by the univariate t-test with 10,000 permutations identified 900 genes that were differentially regulated by at least 4-fold at a p value of <0.001. Unsupervised analysis revealed that when compared to normal endometrium, serous and endometrioid stage I cancers appeared to have similar expression patterns. However, when compared in the absence of normal controls, they were distinct. Differential expression analysis revealed a number of transcripts that were common as well as unique to both histologic types. This data uncovers previously unrecognized, novel pathways involved in early stage endometrial cancers and identifys targets for prevention strategies that are inclusive of both endometrioid and serous histologic subtypes.
Publication Title
Identifier mapping performance for integrating transcriptomics and proteomics experimental results.
Sample Metadata Fields
Age, Disease stage, Race
View Samples- Homo sapiens
- 102 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
The metastatic form of Melanoma has a reported ten-year survival rate of approximately 15%. Clinical trials have shown modest success in a subset of patients. Particularly, combinational therapy using checkpoint blockade has shown the most success, but many patients do not respond. The patients that do respond to treatments often have a pre-existing antitumor immunity.
Publication Title
Dysregulated NF-κB-Dependent ICOSL Expression in Human Dendritic Cell Vaccines Impairs T-cell Responses in Patients with Melanoma.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 56 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
High-grade serous ovarian cancer (HGSOC) is an aggressive disease with few available targeted therapies. Despite high expression of estrogen receptor-alpha (ER) in ~80% of HGSOC and some small but promising clinical trials of endocrine therapy, ER has been understudied as a target in this disease. Results: Proliferation is ER-regulated in HGSOC cells in vitro and in vivo, and is in part dependent on 3-D context. Transcriptomic studies identified genes shared by cell lines and PDX explants as ER targets. The selective ER down-regulator (SERD) fulvestrant is more effective than tamoxifen in blocking ER action. ER H-score was predictive of efficacy of endocrine therapy, and this prediction could be further improved by inclusion of target gene expression, especially that of IGFBP3. Conclusion: Laboratory models corroborate intertumor heterogeneity of endocrine response in HGSOC but identify features associated with functional ER and endocrine responsiveness. Assessing ER function (e.g. IGFBP3 expression) in conjunction with ERH-score may help select patients who would benefit from endocrine therapy. Our preclinical data suggest that SERDs might be more effective than tamoxifen.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples