Gene expression of T47D-MTVL human breast cancer cells expressing Dox-inducible shRNAs against histone H1.4 (120sh) or multiple H1 variants (225sh) Overall design: Stable breast cancer-derived cell lines expressing an shRNA against one of each of the histone H1 isoforms in response to doxycycline (Dox) were grown for six days in the presence or absence of Doxicycline, RNA extracted and high-thorughput sequenced. Cell lines used: inducible shRNA against H1.4 or multiple H1 variants and random shRNA-expression vector.
Histone H1 depletion triggers an interferon response in cancer cells via activation of heterochromatic repeats.
Cell line, Subject
View SamplesWhsc1 gene codes for a SET domain-containing H3K36 dimethylase, whose activity has been suggested, in ex vivo cell culture experiments, to control many aspects of DNA and RNA processing (replication, repair, transcription, etc). Its precise function in vivo is still unclear. Here, we use RNA-seq transcriptome analysis to study the changes in gene expression in the absence of Whsc1. Our results show that, in the experimental system used, loss of Whsc1 caused massive changes in genes affecting many fundamental cellular processes, from cell cycle to ribosome synthesis, DNA repair, replication, etc. Overall design: Whsc1-KO mice are embryonic lethal. We therefore took hematopoietic cells from fetal liver of WT and Whsc1-KO embryo littermates and injected them in to lethally irradiated RAG1-KO recipients and allowed the generation of a full Whsc1-KO hematopoietic system. Then, WT and Whsc1-KO B cells were obtained from the spleen and stimulated with LPS to induce proliferation and class switch recombination. Flow cytometry and cell cycle analyses (among others) showed the existence of serious proliferative alterations in Whsc1-KO cells. Then, we performed paired-end RNAseq analyses of 7 independent WT and 6 independent Whsc1-KO biological replicates and we used these data to identify differentially expressed genes and pathways regulated by Whsc1 in B cells.
Wolf-Hirschhorn Syndrome Candidate 1 Is Necessary for Correct Hematopoietic and B Cell Development.
Cell line, Subject
View SamplesThe high mutation rate of HIV is linked to the generation of viruses expressing proteins with altered function whose impact on disease progression is unknown. We investigated the effects of HIV-1 viruses lacking Env, Vpr and Nef on CD4+ T cell gene expression using high-density DNA microarray analysis and functional assays.
Tat-induced FOXO3a is a key mediator of apoptosis in HIV-1-infected human CD4+ T lymphocytes.
No sample metadata fields
View SamplesHere we tested a hypothesis that epileptogenesis influences expression pattern of genes in the basolateral amygdala that are critical for fear conditioning. Whole genome molecular profiling of basolateral rat amygdala was performed to compare the transcriptome changes underlying fear learning in epileptogenic and control animals. Our analysis revealed that after acquisition of fear conditioning 26 genes were regulated differently in the basolateral amygdala of both groups. Thus, our study provides the first evidence that not only the damage to the neuronal pathways but also altered composition or activity level of molecular machinery responsible for formation of emotional memories within surviving pathways can contribute to impairment in emotional learning in epileptogenic animals. Understanding the function of those genes in emotional learning provides an attractive avenue for identification of novel drug targets for treatment of emotional disorders after epileptogenesis-inducing insult.
Epileptogenesis alters gene expression pattern in rats subjected to amygdala-dependent emotional learning.
No sample metadata fields
View SamplesSurvival of insects on a substrate containing toxic substances such as plant secondary metabolites or insecticides is dependent on the metabolism or excretion of those xenobiotics. The primary sites of xenobiotic metabolism are the midgut, Malpighian tubules and fat body. In general, these organs are treated as single tissues by online databases, but several studies have shown that gene expression within subsections of the midgut is compartmentalized. In this article, RNA sequencing analysis was used to investigate whole-genome expression in subsections of the third-instar larval midgut. The results support functional diversification in subsections of the midgut. Analysis of the expression of gene families that are implicated in the metabolism of xenobiotics suggests that metabolism may not be uniform along the midgut. These data provide a starting point for investigating gene expression and xenobiotic metabolism in the larval midgut. Overall design: Examination of expression in eight samples corresponding to compartments of gene expression in the midgut
Whole-genome expression analysis in the third instar larval midgut of Drosophila melanogaster.
Specimen part, Cell line, Subject
View SamplesProtein inhibitor of activated STAT3 (PIAS3) is an endogenous inhibitor of STAT3 that negatively regulates STAT3 transcriptional activity and cell growth and demonstrates limited expression in the majority of human squamous cell carcinomas of the lung. In the present study we sought to determine if PIAS3 inhibits cell growth in non-small cell lung cancer (NSCLC) cell lines by induction of apoptosis and further determine the dependence of PIAS3 activity on p53 status by using both wild-type and p53-null cells. Our results demonstrate that over-expression of PIAS3 promotes caspase 3 activation and PARP cleavage. Furthermore, the expression of pro-survival family members Bcl-xL and Bcl-2 is decreased. These effects were observed after both transient and regulated expression of exogenous PIAS3 and were independent of p53 status. Furthermore, while p53 can promote apoptosis by inhibition of STAT3 activity, PIAS3 inhibition of STAT3 activity was also p53 independent. Microarray experiments were performed to further investigate the STAT3-dependence of PIAS3-induced apoptosis by comparing the apoptotic gene expression signature induced by PIAS3 over-expression with that induced by STAT3 siRNA. The results showed that a subset of apoptotic genes, including CIDEC and DAPK2, were uniquely expressed only after PIAS3 expression. Thus, PIAS3 may represent a promising lung cancer therapeutic target because of its p53-independent efficacy as well as its potential to synergize with direct STAT3 inhibitors.
PIAS3 activates the intrinsic apoptotic pathway in non-small cell lung cancer cells independent of p53 status.
Specimen part, Cell line
View SamplesRNA sequencing technology has been carried out in order to evaluate mRNA expression changes after manipulation of miR-26a in both MCF-7 and MDA-MB-231 breast cancer cell lines. Overall design: To evaluate the entire set of genes modulated by miR-26a in breast cancer, we performed RNA-seq after ectopic manipulation of this miRNA. We over-expressed miR-26a in MCF-7 epithelial cancer cell lines and also reduced its activity by stably transfecting MDA-MB-231 mesenchymal-like cancer cell lines with a specific sponge vector. GO terms and pathway enriched analysis of the transcripts that significantly change upon miR-26 ectopic manipulation implicates miR-26ab in cell cycle, apoptosis, cell spreading and cell adhesion in breast cancer
Sustained expression of miR-26a promotes chromosomal instability and tumorigenesis through regulation of CHFR.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
DNA methylation status is more reliable than gene expression at detecting cancer in prostate biopsy.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Invasive lobular carcinoma cell lines are characterized by unique estrogen-mediated gene expression patterns and altered tamoxifen response.
Specimen part, Cell line, Treatment, Time
View SamplesInvasive lobular carcinoma (ILC) is a histological subtype of breast cancer that is frequently associated with favorable outcomes, as ~90% of ILC express the estrogen receptor (ER). However, recent retrospective analyses suggest that ILC patients receiving adjuvant endocrine therapy may not benefit from improved outcomes versus other breast cancer patients. Based on these observations, we characterized ER function and endocrine response in ILC models. The ER-positive ILC cell lines MDA MB 134VI (MM134) and SUM44PE were used to examine the ER-regulated transcriptome in vitro via gene expression microarray analyses and ER ChIP-Seq. In parallel, estrogen response was assessed in vivo in the patient-derived ILC xenograft HCI-013. Response to endocrine therapy was also examined in ILC cell lines. We identified 915 genes that were uniquely E2-regulated in ILC cell lines versus other breast cancer cell lines, and a subset of these genes were also regulated in vivo in HCI-013. We observed that MM134 were de novo tamoxifen resistant, and were induced to grow by 4-hydroxytamoxifen, as well as other anti-estrogens, as partial agonists. Growth was accompanied by agonist activity of tamoxifen on ER-mediated gene expression. Though tamoxifen induced cell growth, MM134 cells required FGFR1 signaling to maintain viability and were sensitive to combined endocrine therapy and FGFR1 inhibition. Our observation that ER drives a unique program of gene expression in ILC cells correlates with the ability of tamoxifen to induce growth in these cells. Targeting growth factors using FGFR1 inhibitors may block survival pathways required by ILC and reverse tamoxifen resistance.
Invasive lobular carcinoma cell lines are characterized by unique estrogen-mediated gene expression patterns and altered tamoxifen response.
Specimen part, Cell line, Treatment, Time
View Samples