HOX genes encode a family of homeodomain-containing transcription factors involved in the determination of cell fate and identity during embryonic development. They also behave as oncogenes in some malignancies. In this study, we found high expression of the HOXD9 gene transcript in glioma cell lines and human glioma tissues by quantitative real-time PCR. Using immunocytochemistry, we observed HOXD9 protein expression in human brain tumor tissues, including astrocytomas and glioblastomas. To investigate the role of HOXD9 in gliomas, we silenced its expression in the glioma cell line U87 using HOXD9-specific siRNA, and observed decreased cell proliferation, cell cycle arrest, and induction of apoptosis. It was suggested that HOXD9 contributes to both cell proliferation and/or cell survival. The HOXD9 gene was highly expressed in a side population (SP) of SK-MG-1 cells that was previously identified as an enriched-cell fraction of glioma cancer stem-like cells. HOXD9 siRNA treatment of SK-MG-1 SP cells resulted in reduced cell proliferation. Finally, we cultured human glioma cancer stem cells (GCSCs) from patient specimens found with high expression of HOXD9 in GCSCs compared with normal astrocyte cells and neural stem/progenitor cells (NSPCs). Our results suggest that HOXD9 may be a novel marker of GCSCs and cell proliferation and/or survival factor in gliomas and glioma cancer stem-like cells, and a potential therapeutic target.
Functional analysis of HOXD9 in human gliomas and glioma cancer stem cells.
Cell line
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The intracellular domain of teneurin-1 induces the activity of microphthalmia-associated transcription factor (MITF) by binding to transcriptional repressor HINT1.
Cell line
View SamplesWe identified histidine triad nucleotide binding protein 1 (HINT1) as a human teneurin-1 ICD interaction partner in a yeast-2 hybrid screen. This interaction was confirmed in human cells, where HINT1 is known to inhibit the transcription of target genes by directly binding to transcription factors at the promoter. In a whole transcriptome analysis of BS149 glioblastoma cells overexpressing the teneurin-1 ICD, several microphthalmia-associated transcription factor (MITF) target genes were found to be up-regulated. Interestingly, MITF is one of the transcription factors inhibited by HINT1. Thus, we directly compare the transcriptomes of MITF versus TEN1-ICD overexpressing BS149 cells in this study, in order to reveal any co-regulated genes.
The intracellular domain of teneurin-1 induces the activity of microphthalmia-associated transcription factor (MITF) by binding to transcriptional repressor HINT1.
Cell line
View SamplesTeneurins are large type II transmembrane proteins that are necessary for the normal development of the central nervous system (CNS). While many studies highlight the significance of teneurins, especially during development, there is only limited information known about the molecular mechanisms of function. Previous studies have shown that the N-terminal intracellular domain (ICD) of teneurins can be cleaved at the membrane and subsequently translocates to the nucleus where it can influence gene transcription. Target genes as well as mechanisms have yet to be elucidated, and thus we are investigating the transcriptional activity of the human teneurin-1 ICD in this study.
The intracellular domain of teneurin-1 induces the activity of microphthalmia-associated transcription factor (MITF) by binding to transcriptional repressor HINT1.
Cell line
View SamplesPost-traumatic stress disorder is a concerning psycho behavioral disorder thought to emerge from the complex interaction between genetic and environmental factors. For soldiers exposed to combat, the risk of developing this disorder is two-fold and diagnosis is often late, when much sequela has set in. To be able to identify and diagnose in advance those at “risk” of developing PTSD, would greatly taper the gap between late sequelae and treatment. Therefore, this study sought to test the hypothesis that the transcriptome can be used to track the development of PTSD in this unique and susceptible cohort of individuals. Gene expression levels in peripheral blood samples from 85 Canadian infantry soldiers (n = 58 subjects negative for PTSD symptoms and n = 27 subjects with PTSD symptoms) were determined by RNA sequencing technology following their return from deployment to Afghanistan. Count-based gene expression quantification, normalization and differential analysis (with thorough correction for confounders) revealed significant differences in two genes, LRP8 and GOLM1 . These preliminary results provide a proof-of-principle for the diagnostic utility of blood-based gene expression profiles for tracking symptoms of post-traumatic stress disorder in soldiers returning from tour. It is also the first to report transcriptome-wide expression profiles alongside a post-traumatic symptom checklist. Overall design: Peripheral blood samples from 85 Canadian infantry soldiers (n = 58 subjects negative for PTSD symptoms and n = 27 subjects with PTSD symptoms)
Using Next-Generation Sequencing Transcriptomics To Determine Markers of Post-traumatic Symptoms: Preliminary Findings from a Post-deployment Cohort of Soldiers.
Sex, Subject
View SamplesSignal transduction processes mediated by phosphatidyl inositol phosphates affect a broad range of cellular processes such as cell cycle progression, migration and cell survival. The protein kinase AKT is one of the major effectors in this signaling network. Chronic AKT activation contributes to oncogenic transformation and tumor development. Therefore, new small drugs were designed to block AKT activity for cancer treatment.
Characterization of AKT independent effects of the synthetic AKT inhibitors SH-5 and SH-6 using an integrated approach combining transcriptomic profiling and signaling pathway perturbations.
Specimen part, Cell line
View SamplesA series of transfections was performed in Drosophila S2 cells to explore: 1) the types of target sites that Drosophila microRNAs recognize, 2) the relative functional efficacy of these sites in mediating repression, and 3) the determinants that allow some sites to have greater potency than others. 3p-seq was also performed to help reannotate and quantify the landscape of 3'' UTRs in Drosophila S2 cells. Overall design: Nine mRNA profiles were generated, with Drosophila S2 cells transfected with one of 6 microRNAs (miR-1, miR-4, miR-92a, miR-124, miR-263a, and miR-997). These samples were compared to 3 biological replicates of a mock transfection condition. 3p-seq data for S2 cells was also generated to help reannotate and quantify 3'' UTR isoforms.
Predicting microRNA targeting efficacy in Drosophila.
Specimen part, Subject
View SamplesThe objective of the present study was to identify genes that are involved in increasing the ovulation number in mouse line FL1 that had been selected for high fertility performance.
Expression profiling of a high-fertility mouse line by microarray analysis and qPCR.
No sample metadata fields
View SamplesmRNA expression levels in synovial fibroblasts in 6 rheumatoid arthritis patients versus 6 osteoarthritis patients.
Constitutive upregulation of the transforming growth factor-beta pathway in rheumatoid arthritis synovial fibroblasts.
No sample metadata fields
View SamplesAcute myeloid leukemia (AML) is a heterogeneous disease and AML with normal karyotype (AML-NK) is categorized as an intermediate-risk group. Over the past years molecular analyses successfully identified biomarkers that will further allow to dissecting clinically meaningful subgroups in this disease. Thus far, somatic mutations were identified which elucidate the disturbance of cellular growth, proliferation, and differentiation processes in hematopoietic progenitor cells. In AML-NK, acquired gene mutations with prognostic relevance were identified for FLT3, CEBPA, and NPM1. FLT3-ITD mutations were associated with short relapse-free and overall survival, while mutations in CEBPA or NPM1 (without concomitant FLT3-ITD) had a more favorable outcome.
Quantitative comparison of microarray experiments with published leukemia related gene expression signatures.
Sex, Age, Disease, Disease stage
View Samples