Relation between microRNA expression and EGFR amplification status
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Daniel Monleon
PROVIDER: E-MTAB-2478 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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2016-04-15 | PXD002783 | Pride
Project description:The aim of this study was to determine the relationship between gene expression profiles and new metabolic subgroups of benign meningioma with potential clinical relevance. 19 human meningiomas biopsies were obtained at the Department of Neurosurgery of the Clinical University Hospital of Valencia. This study was reviewed and approved by the local ethics committee. During surgery, most of the resected tissue was sent for routine histological analysis and the remainder was immediately put in cryogenic vials and snap-frozen in liquid nitrogen. All snap-frozen samples were stored in a freezer at -80 C until further analysis. Tumors were classified according to the 2007 WHO Histological Classification 1. Grade II meningioma were classified according to previously published criteria, including high mitotic index and three out of five markers of atypia.In summary, this work demonstrates gene expression differences in a new subgroup of histological benign meningiomas that exhibit aggressive metabolism and tumor recurrence.
2012-08-31 | E-MEXP-3586 | biostudies-arrayexpress
Project description:To comprehensively characterize microRNAs (miRNA) expression and their target genes in thyroid cancer, we performed next-generation sequencing expression analysis of this disease. Recent studies have found that only the most abundant microRNAs mediate significant target suppression. We sequenced small RNA from 8 papillary thyroid carcinomas (PTC) with paired samples of normal thyroid tissue. We found that only a small set of abundant miRNAs are differentially expressed after pair-wise comparison (12 upregulated and 8 downregulated) reaching the minimum threshold amount to repress target mRNAs. We integrated computational prediction of potential targets and mRNA sequencing from the paired normal and tumor thyroid tissues from the same eight patients with PTC. The integrated analyses identified a master microRNA regulatory network in PTC that is involved in essential biological processes such as thyroid differentiation. As both mature products of miR-146b (miR-146b-5p and -3p) were among the most abundant upregulated in tumors, we unveil their target genes and found that miR-146b-3p specifically binds to the 3`UTR of PAX8 and NIS, leading to an impaired translation of the proteins and subsequently decreasing the iodide uptake of the cells. Furthermore, we show that mir-146b and PAX8 regulate each other, describing a novel regulatory circuit that determines the differentiated phenotype of PTC. In conclusion, our integrative genomic analysis uncovers the target genes of two of the most upregulated miRNAs and highlights the importance of a miR-146b3p-PAX8-NIS regulatory circuit that determines thyroid differentiation in thyroid cancer. Samples from Papillary Thyroid Carcinoma tumors (n=8) and contralateral normal thyroid tissue from the same patient (n=8) were collected at the Biobank of the Hospital Universitario La Paz (Madrid, Spain). The clinical characteristics of patients are summarized in Table S1. Surgically removed tissues were quickly frozen in liquid nitrogen until analysis. The samples were snap frozen on dry ice and stored at -80°C.
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2015-01-08 | E-GEOD-64751 | biostudies-arrayexpress
Project description:The recent incorporation of molecular features into the diagnosis of Glioblastoma Multiforme patients has led to an improved categorisation into different tumour subtypes with different prognosis and disease management. In this work, we have exploited the benefits of genome-wide multiomic approaches to identify potential molecular vulnerabilities existing on GBM patients. We used the Illumina MethylationEPIC Beadchip platform to describe the genome-wide 5mC and 5hmC DNA methylation landscape of a total of 9 patient-derived Glioblastoma Multiforme Cell lines obtained from the human glioblastoma cell culture resource (HGCC) and 4 brain samples obtained from non-tumoral controls
2023-06-01 | E-MTAB-12473 | biostudies-arrayexpress
Project description:Background: Newer 3D culturing approaches are a promising way to better mimic the in vivo tumor microenvironment and to study the interactions between the heterogeneous cell populations of glioblastoma multiforme. Like many other tumors, glioblastoma uses extracellular vesicles as an intercellular communication system to prepare surrounding tissue for invasive tumor growth. However, little is known about the effects of 3D culture on extracellular vesicles. The aim of this study was to comprehensively characterise extracellular vesicles in 3D organoid models and compare them to conventional 2D cell culture systems.Methods: Primary glioblastoma cells were cultured as 2D and 3D organoid models. Extracellular vesicles were obtained by precipitation and immunoaffinity, with the latter allowing targeted isolation of the CD9/CD63/CD81 vesicle subpopulation. Comprehensive vesicle characterisation was performed and miRNA expression profiles were generated by smallRNA-sequencing. In silico analysis of differentially regulated miRNAs was performed to identify mRNA targets and corresponding signaling pathways. The tumor cell media and extracellular vesicle proteome were analysed by high-resolution mass spectrometry.Results: We observed an increased concentration of extracellular vesicles in 3D organoid cultures. Differential gene expression analysis further revealed the regulation of twelve miRNAs in 3D tumor organoid cultures (with nine miRNAs down and three miRNAs upregulated). MiR-23a-3p, known to be involved in glioblastoma invasion, was significantly increased in 3D. MiR-7-5p, which counteracts glioblastoma malignancy, was significantly decreased. Moreover, we identified four miRNAs (miR- 323a-3p, miR-382-5p, miR-370-3p, miR-134-5p) located within the DLK1-DIO3 domain, a cancer associated genomic region, suggesting a possible importance of this region in glioblastoma progression. Overrepresentation analysis identified alterations of extracellular vesicle cargo in 3D organoids, including representation of several miRNA targets and proteins primarily implicated in the immune response.Conclusion: Our results show that 3D glioblastoma organoid models secrete extracellular vesicles with an altered cargo compared to corresponding conventional 2D cultures. Extracellular vesicles from 3D cultures were found to contain signaling molecules associated with the immune regulatory signaling pathways and as such could potentially change the surrounding microenvironment towards tumor progression and immunosuppressive conditions. These findings suggest the use of 3D glioblastoma models for further clinical biomarker studies as well as investigation of new therapeutic options.
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Project description:Analysis of human glioblastoma multiforme tumors revealed genes that are upregulated in tumors expressing EGFRvIII compared to those expressing wild-type EGFR We examined gene expression in 52 primary GBM tumors, which were stratified based on the presence or absence of EGFRvIII expression using EGFRvIII-specific RT-PCR (Tykocinski et al., 2012). The extracted RNA samples from these tumors were subjected to microarray analysis using HG-U133 2.0 Plus Affymetrix gene chips. Average expression of all transcripts were compared between EGFRvIII-positive and -negative GBMs.
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Project description:Temporal lobe epilepsy (TLE) is the most frequent type of focal epilepsy in adults, typically resistant to pharmacological treatment and mostly present with cognitive impairment and psychiatric comorbidities. The most common neuropathological hallmark in TLE patients is hippocampal sclerosis(HS). However, the underlying molecular mechanisms involved remain poorly characterized. Dentate gyrus(DG), one specific hippocampal subarea, structural and functional changes imply a key involvement of the DG in the development of TLE. In this study, isobaric tags for relative and absolute quantitation (iTRAQ) -based quantitative proteomic technique was performed to analysis of hippocampal DG obtained from patients with TLE-HS compared to control samples obtained from the autopsy. Our proteomic data identified 5583 proteins, of which 82 proteins were up-regulated and 90 proteins were down-regulated. Bioinformatics analysis indicated that differential expressed proteins enriched in “synaptic vesicle”, “mitochondrion”, “cell-cell adhesion”, “regulation of synaptic plasticity”, “ATP binding” and “Oxidative phosphorylation”. Protein-protein interaction network analysis found a pivotal module of 10 proteins that relate to “Oxidative phosphorylation”. This study is the first to investigate proteomic alterations in DG region of TLE-HS patients, and pave the way to better understanding of epileptogenesis mechanisms and future therapeutic intervention.
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