The aim of this study was to measure the influence of beverages on blood gene expression. We wanted to explore the underlying mechanisms of the cardioprotective effects of red wine.
Analysis with respect to instrumental variables for the exploration of microarray data structures.
No sample metadata fields
View SamplesInnovative approaches combining regulatory networks and genomic data are needed to extract pertinent biological informations to a better understanding of complex disease such as cancer and improve identi cation of entities leading to potential new therapeutic avenues. In this study, we confronted an automatic generated regulatory network with gene expression pro les (GEP) from a large cohort of patients with multiple myeloma (MM) and normal individuals with a causality reasonning method based of graph coloring to identify keynodes. Due to this causality reasoning, it is possible to infer proteins state from these GEP. Also, our method is able to simulate the impact of the perturbation of a node in this regulatory network to identify therapeutic targets. This method allowed us to nd that JUN/FOS and FOXM1, known in MM, and their inhibition as speci c to large group of patients with MM. Moreover, we associated the inhibition of FOXM1 activity with good prognosis, suggesting the inhibition of FOXM1 activity could be a survival marker. Finally, if JUN/FOS activation seems to be a way to strongly perturb the regulatory network in view of GEP, our result suggests the activation of FOXM1 could be interesting way to perturb some sub-group of profiles.
Logic programming reveals alteration of key transcription factors in multiple myeloma.
Specimen part, Disease, Disease stage
View SamplesIn this study we addressed subclonal evolutionary process after treatment and subsequent relapse in multiple myeloma (MM) in a cohort of 24 MM patients treated either with conventional chemotherapy or with the proteasome inhibitor, bortezomib. Because MM is a highly heterogeneous disease coupled with a large number of DNA copy number alterations (CNAs) and loss of heterozygosity (LOH), we focused our study on the secondary genetic events: 1q21 gain, NF-kB activating mutations, RB1 and TP53 deletions, that seem to reflect progression. By using genome-wide high resolution SNP arrays we identified subclones with nonlinear complex evolutionary histories in a third of patients with myeloma, the relapse clone apparently derived from a minor subclone at diagnosis. Such reordering of the spectrum of genetic lesions during therapy is likely to reflect selection of genetically distinct subclones not initially competitive against the dominant population that survived chemotherapy, thrived and acquired new anomalies. In addition we found that emergence of minor subclones at relapse was significantly associated with bortezomib treatment. Altogether, these data support the idea of new strategy of future clinical trials in MM that would combine targeted therapy and subpopulations control to eradicate all myeloma subclones in order to obtain long-term remission.
Minor clone provides a reservoir for relapse in multiple myeloma.
Specimen part, Disease, Cell line, Subject
View SamplesSeries GSE25262 patients on expression side.
Minor clone provides a reservoir for relapse in multiple myeloma.
Specimen part, Disease
View SamplesHMGN1 contributes to the shortened latency of liver tumorigenesis by changing a chromatin structure and expression of relevant genes
Loss of the nucleosome-binding protein HMGN1 affects the rate of N-nitrosodiethylamine-induced hepatocarcinogenesis in mice.
Specimen part, Treatment
View SamplesTotal RNA extracted from prostate cancer LNCaP cells transfected with siRNA against CTCF(siCTCF), or negative control siRNA (si-)were processed, and sequenced by two different companies using Illumina Hi-seq 2000 platform to generate RNA sequencing with two output sequences: paired-end 50bp and 101bp in read length. Nearly 100 million and 50 million raw reads were yielded from each sample respectively. We used FastQC to confirm the quality of raw fastq sequencing data, and SOAPfuse software to detect fusion transcripts. Overall design: Discovering fusion genes from siCTCF and si- in LNCaP cells.
Discovery of CTCF-sensitive Cis-spliced fusion RNAs between adjacent genes in human prostate cells.
No sample metadata fields
View SamplesTranscriptomic changes in human liver cancer cell lines caused by the demethylating drug zebularine.
An integrated genomic and epigenomic approach predicts therapeutic response to zebularine in human liver cancer.
Cell line
View SamplesAlthough epigenetic mechanisms, such as specific histone modifications, control common and cell-specific genetic programs, a role for histone modifying enzymes in liver metabolism and disease has not been investigated. This report demonstrates that the combined loss of the histone methyltransferases EZH1 and EZH2 in mouse hepatocytes led to the disruption of H3K27me3 homeostasis by age three months, simple fatty liver by age six months and fatal fibrosis by age 15 months. Global and gene-specific reduction of H3K27me3 marks paralleled a concomitant increase of H3K4me3 marks at genes associated with chronic liver disease. Advanced disease was accompanied by widespread infiltration of immune cells, an increase of activated hepatic stellate cells and collagen deposition. Expression of genes from the cytochrome P450 family that control drug metabolism was already deregulated by age two months and mice were fatally hypersensitive to carbon tetrachloride (CCl4). These genetic experiments, for the first time, illustrate that the simple loss of EZH1/EZH2, which results in the disruption of epigenetic modifications, is sufficient for the progression of fatal liver disease. Overall design: RNA-seq and ChIP-seq were performed in liver tissues.
The methyltransferases enhancer of zeste homolog (EZH) 1 and EZH2 control hepatocyte homeostasis and regeneration.
No sample metadata fields
View SamplesThe tumor suppressor BRCA1 regulates DNA damage responses and multiple other processes. Among these, BRCA1 heterodimerizes with BARD1 to ubiquitylate targets via its N-terminal RING domain. Here we show that BRCA1 promotes oxidative metabolism via degradation of Oct1, a transcription factor with pro-glycolytic/tumorigenic effects. BRCA1 E3 ubiquitin ligase mutation skews cells towards a glycolytic metabolic profile while elevating Oct1 protein. CRISPR-mediated Oct1 deletion reverts the glycolytic phenotype. RNAseq confirms the deregulation of metabolic genes. BRCA1 mediates direct Oct1 ubiquitylation and degradation, and mutation of two ubiquitylated Oct1 lysines insulates the protein against BRCA1-mediated destabilization. Oct1 deletion in MCF-7 breast cancer cells does not perturb growth in standard culture, but inhibits growth in soft agar and xenografts. Oct1 protein levels correlate positively with tumor aggressiveness, and inversely with BRCA1, in primary breast cancer samples. These results identify BRCA1 as an Oct1 ubiquitin ligase that catalyzes Oct1 degradation to promote oxidative metabolism. Overall design: mRNA profiles of BRCA1-I26A mutant MEFs treated with control CRISPR lentiviral vector, or an Oct1-specific CRISPR construct
BRCA1 through Its E3 Ligase Activity Regulates the Transcription Factor Oct1 and Carbohydrate Metabolism.
Specimen part, Cell line, Subject
View SamplesFailures to produce neutralizing antibodies upon HIV-1 infection result in part from B cell dysfunction due to unspecific B cell activation. How HIV-1 affects antigen-specific B cell functions remains elusive. Using an adoptive transfer mouse model and ex vivo HIV infection of human tonsil tissue we found that expression of the HIV-1 pathogenesis factor NEF in CD4 T cells undermines their helper function and impairs cognate B cell functions including mounting of efficient specific IgG responses. NEF interfered with T cell help via a specific protein interaction motif that prevents polarized cytokine secretion at the T cell - B cell immune synapse. This interference reduced B cell activation and proliferation and thus disrupted germinal center formation and affinity maturation. These results identify NEF as a key component for HIV-mediated dysfunction of antigen-specific B cells. Therapeutic targeting of the identified molecular surface in NEF will facilitate host control of HIV infection.
HIV-1 infection of CD4 T cells impairs antigen-specific B cell function.
Specimen part
View Samples