Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA273797 | ENA |
REPOSITORIES: ENA
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Project description:The transcription factor, NF-кB, plays a central role in the response to DNA damage. This ubiquitous family of proteins is made up of five subunits: p50 (NF-κB1, p105), p52 (NF-κB2, p100), p65 (relA), relB, and crel that appear in their mature form as dimers. Following stimulation, NF-κB dimers translocate to the nucleus where they bind specific consensus elements (κB-sites) in the promoter region of genes involved in cell survival, inflammation and the immune system. While there is a general propensity of NF-кB to mediate survival, this is not always the case and several reports note the pro-apoptotic nature of the NF-кB pathway. In examining the NF-кB response to DNA damage, we have found that the p50 subunit plays a central role in modulating cytotoxicity following TMZ treatment in malignant glioma. In the current study, given the importance of p50 to the cytotoxic response to TMZ, we set out to identify NF-кB-dependent factors that modulate the response to TMZ. U-87 glioma cells stably transfected with either control-shRNA or p105-shRNA and subsequently treated with temozolomide (TMZ) were selected for RNA extraction and hybridization on Affymetrix microarrays. Each category contains 3 biologic replicates.
2015-01-29 | E-GEOD-65363 | biostudies-arrayexpress
Project description:Acquired resistance of temozolomide (TMZ) is one of the major obstacle of glioblastoma clinical treatment and the mechanism of TMZ resistance is still not very clear. In the presented research we show that deletion of rs16906252-associated MGMT enhancer in MGMT negative glioma cells induced increase sensitivity to temozolomide and combination of RNA-seq and Capture HiC identified several long-range target genes of rs16906252-associated MGMT enhancer. In addition, HiC data shows alterations of chromatin structures in glioma cells survived from high-dosage TMZ treatment and changes of TADs influence rs16906252-associated MGMT enhancer’s long-range regulations of target genes. Our study suggests rs16906252-associated MGMT enhancer regulates glioma cells’ TMZ sensitivity by long-range regulations of several target genes, which is a novel mechanism of regulation of TMZ sensitivity in glioma cells.
2020-04-02 | GSE129476 | GEO
Project description:Expression data from STAG2 deficient and proficient human cancer cells
| PRJNA139663 | ENA
Project description:to investigate the sensitization mechanism of temozolomide-resistant U-87 cells by evernic acid, we established gene expression of U-87 cells treated with evernic acid, temozolomide and their combinations compared to the gene expression of untreated cells. The NGS-core facility of the University Hospital Bonn of Bonn University performed the RNA-sequencing.
2023-10-24 | GSE245919 | GEO
Project description:The combination of bevacizumab with temozolomide and radiotherapy was shown to prolong progression-free survival in newly diagnosed glioblastoma patients, and this emphasizes the potential of bevacizumab as a glioma treatment. However, while bevacizumab effectively inhibits angiogenesis, it has also been reported to induce invasive proliferation. This study examined gene expression in glioma cells to investigate the mechanisms of bevacizumab-induced invasion. We made a human glioma U87ΔEGFR cell xenograft model by stereotactically injecting glioma cells into the brain of animals. We administered bevacizumab intraperitoneally three times per week. At 18 days after tumor implantation, the brains were removed for histopathology and mRNA was extracted. In vivo, bevacizumab treatment increased glioma cell invasion. qRT-PCR array analysis were perfomed.
2019-02-07 | GSE126168 | GEO
Project description:Transcriptional profiling of glioma cells comparing control U87(Temozolomide sensitive) cells with U87R(Temozolomide resistant). The U87 cell line was given a low dose of temozolomide in culture media for 3 weeks, resulting in the formation of temozolomide-resistant cells made as U87R.
2023-03-01 | GSE193957 | GEO
Project description:To understand the mechanistic insights on how KDM1A inhibition sensitizes glioblastoma (GBM) to temozolomide, we performed genome wide localization studies of KDM1A in patient derived glioma stem cells (GSCs) using CUT&Tag-seq. GSC082209 (GSC08) cells were treated with vehicle or NCD38 (5 μM) for 24 h and 250,000 cells per condition were used. Data analysis on CUT&Tag sequencing reads was performed by the nf-core/cutandrun bioinformatic analysis pipeline. We detected 75,491 KDM1A peaks in the genome of GSCs (p<0.0001). Pathway analysis of KDM1A binding genes using Gene Ontology showed KDM1A binding genes were enriched in DNA repair, cell cycle, and UPR signaling pathways . CUT&Tag sequencing for KDM1A in patient derived glioma stem cells.
2023-02-01 | GSE223280 | GEO
Project description:Overexpression of histone deacetylases (HDACs) in cancer commonly causes resistance to genotoxic based therapies. Here we report on the novel mechanism whereby overexpressed class I HDACs increase the resistance of glioblastoma cells to the SN1 methylating agent temozolomide (TMZ). The chemotherapeutic TMZ triggers the activation of the DNA damage response (DDR) in resistant glioma cells, leading to DNA lesion bypass and cellular survival. Mass spectrometry analysis revealed that the catalytic activity of class I HDACs stimulates the expression of the E3 ubiquitin ligase RAD18. Furthermore, the data show that RAD18 is part of the O6-methylguanine-induced DDR as TMZ induces the formation of RAD18 foci at sites of DNA damage. Downregulation of RAD18 by HDAC inhibition prevents glioma cells from activating the DDR upon TMZ exposure. Lastly, RAD18 or O6-methylguanine-DNA methyltransferase (MGMT) overexpression abolishes the sensitization effect of HDAC inhibition on TMZ-exposed glioma cells. Our study describes the mechanism whereby class I HDAC overexpression in glioma cells causes resistance to TMZ treatment. HDACs accomplish this by promoting the bypass of O6-methylguanine DNA lesions via enhancing RAD18 expression. It also provides a treatment option with HDAC inhibition to undermine this mechanism.
2022-04-01 | PXD028683 | Pride
Project description:Temozolomide (TMZ) resistance of glioma cells is currently a critical problem in glioma clinical treatment. In this study, we reveal a bivalent function of a super-enhancer RNA LINC02454 in modulating glioma cell sensitivity to TMZ via regulation of SORBS2 and DDR expression. LINC02454 increased TMZ sensitivity by maintaining 3D chromatin structure and promoting SORBS2 expression, but paradoxically decreased TMZ sensitivity by binding to the DDR1 locus and promoting DDR1 transcription. This study proposes a new regulatory mechanism governing glioma cell sensitivity to TMZ and provides new insights that may improve therapies against glioma.
2024-01-10 | GSE229600 | GEO
Project description:Introduction: Glioma stem cells isolated from human glioblastomas are resistant to radiation and cytotoxic chemotherapy and may drive tumor recurrence. Treatment efficacy may depend on the presence of glioma stem cells, expression of DNA repair enzymes such as methylguanine methyltransferase (MGMT), or transcriptome subtype. Methods: To model genetic alterations in the core signaling pathways of human glioblastoma, we induced conditional Rb knockout, Kras activation, and Pten deletion mutations in cortical murine astrocytes. Serial neurosphere culture, multi-lineage differentiation, and orthotopic transplantation were used to assess whether these mutations induced de-differentiation of cortical astrocytes into glioma stem cells. Efficacy of radiation and temozolomide was examined in vitro and in an allograft model in vivo. The effects of radiation on transcriptome subtype was examined by expression profiling. Results: G1/S-defective, Rb knockout astrocytes gained unlimited self-renewal and multi-lineage differentiation capacity, in both the presence and absence of Kras and Pten mutations. Only triple mutant astrocytes formed serially-transplantable glioblastoma allografts. Triple mutant astrocytes and allografts were sensitive to radiation, but expressed Mgmt and were resistant to temozolomide. Radiation induced a shift in transcriptome subtype of glioblastoma allografts from proneural to mesenchymal. Conclusion: A defined set of core signaling pathway mutations induces de-differentiation of cortical murine astrocytes into glioma stem cells. This non-germline genetically engineered mouse model mimics human proneural glioblastoma on histopathological, molecular, and treatment response levels. It may be useful in dissecting the genetic and cellular mechanisms of treatment resistance and developing more effective therapies.
2016-02-01 | GSE75589 | GEO