Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA393012 | ENA |
REPOSITORIES: ENA
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Project description:Glioblastoma multiforme(GBM) is the most common and lethal malignant primary brain tumor. Temozolomide (TMZ) is a promising chemo-therapeutic agent to treat GBM. However, resistance to TMZ develops quickly with a high frequency. The mechanisms underlying GBM cells’ resistance to TMZ are not fully understood. Non-coding RNAs are aberrantly expressed in many cancers and are highly involved in their pathogenesis including drug-resistence. In order to systematically study the role of miRNAs in GBM cells' resistence to TMZ , we built gene expression profiles of TMZ-resistant cell line and TMZ-sensitive cell line using miRNA gene expression microarrays.
2020-07-04 | GSE100775 | GEO
Project description:mRNA expression data from TMZ-resistant cell line
| PRJNA768121 | ENA
Project description:LncRNA and mRNA expression data from TMZ-resistant cell line
| PRJNA392890 | ENA
Project description:Glioblastoma multiforme (GBM) is the most common and lethal malignant primary brain tumor. Temozolomide (TMZ) is a promising chemo-therapeutic agent to treat GBM. However, resistance to TMZ develops quickly with a high frequency. The mechanisms underlying GBM cells’ resistance to TMZ are not fully understood. Long non-coding RNAs (lncRNAs) are aberrantly expressed in many cancers and are highly involved in their pathogenesis including drug-resistence. In order to systematically study the role of lncRNAs in GBM cells' resistence to TMZ , we built gene expression profiles of TMZ-resistant cell line and TMZ-sensitive cell line using lncRNA and mRNA gene expression microarrays.
2020-07-03 | GSE100736 | GEO
Project description:Glioblastoma (GBM) is an aggressive brain cancer that is notoriously resistant to chemotherapy, particularly to Temozolomide (TMZ). In this study, we examined a patient-derived TMZ-resistant GBM cell line and assessed the effects of the PARP inhibitor Olaparib. We observed that while Olaparib exhibited significant tumor inhibition, its required dosage exceeded clinically acceptable levels. Transcriptomic analysis revealed a notable upregulation of nicotinamide phosphoribosyltransferase (NAMPT) in the surviving tumor cells, suggesting that increased intracellular NAD+ levels contributed to their resistance against both Olaparib and TMZ. By optimizing the dosages of Olaparib and FK866, a NAMPT inhibitor, we were able to develop a combination therapy that effectively killed TMZ-resistant GBM cells while adhering to clinically applicable pharmacodynamic and toxicological standards for each drug. This combination was also tested across other TMZ-resistant cell lines and 3D organoids, showing promising potential for clinical application. Additionally, through profiling plasma-detectable circRNA species from the combination treatment, we identified circPTTG1IP as a potential biomarker with negative predictive value. Further analysis indicated that circPTTG1IP might regulate NAMPT expression and NAD+ levels, potentially through its interaction with miRNAs targeting NAMPT. This research provides insights into a novel therapeutic strategy for overcoming TMZ resistance in GBM.
2025-06-02 | GSE295766 | GEO
Project description:cell culture:The human glioma cell line U87MG was obtained from the Cell Resource Center, Peking Union Medical College (Beijing, China), and U251MG was acquired from the American Type Culture Collection (Manassas, VA). Temozolomide (TMZ) resistant U87MG cells (U87TR) and TMZ resistant U251MG cells (U251TR) of glioblastoma (GBM) sub-cell lines, were established through repetitive exposure to increasing TMZ concentrations in vitro in our laboratory. Cells were cultured in DMEM culture medium supplemented with 10% FBS with a standard humidified incubator under 5% CO2 at 37°C.
2023-05-01 | GSE151680 | GEO
Project description:A critical issue is that recurrent glioblastoma multiforme (GBM) after temozolomide (TMZ) exposure becomes more malignant, exhibiting higher invasion and stemness than the primary tumor. However, the detailed mechanism remains to be elucidated. While the majority of GBM cells succumb to TMZ treatment, some enter cell cycle arrest, adopt a senescence-associated secretory phenotype (SASP), and activate senescence-related signaling pathways. These cells later exit senescence, re-enter the cell cycle, and proliferate, forming aggregates with stemness characteristics, including high expression of stemness markers, colony formation, high invasion, migration, and chemotherapy resistance. Critically, these new aggregates promote the invasion, migration, and chemotherapy resistance of surrounding cells. Gene Set Enrichment Analysis (GSEA) and KEGG analysis of miRNA and mRNA sequences indicated that hallmark-hypoxia and HIF1-signaling pathways were activated. We verified that HIF1α and HIF2α levels changed before, during, and after TMZ treatment. Knocking out HIF1α and HIF2α in GBM cells and exposing them to TMZ resulted in fewer senescent cells and aggregates. This study clarifies how recurrent GBM becomes more malignant during and after TMZ treatment and highlights the regulatory roles of HIF1α and HIF2α, emphasizing that preventing senescence cell formation and inhibiting HIF1α and HIF2α expression are crucial for improving therapeutic outcomes.
2025-05-07 | PXD058156 | Pride
Project description:Expression data from WIF1 induced LN-229 (GBM cell line)
| PRJNA252828 | ENA
Project description:Glioblastoma (GBM) carries a dismal prognosis largely due to acquired resistance to the standard treatment, which incorporates the chemotherapy temozolomide (TMZ). Inhibiting the proteasomal pathway is an emerging strategy, where combination treatments are under clinical investigation. We hypothesized that pre-treatment of GBM with bortezomib (BTZ) might sensitize glioblastoma to TMZ by abolishing autophagy survival signals to augment DNA damage and apoptosis. P3 patient-derived GBM cells as well as the tumor cell lines U87, HF66, A172 and T98G were investigated for clonogenic survival after single or combined treatment with TMZ and BTZ in vitro. Change in autophagic flux was examined after experimental treatments in conjunction with inhibitors of autophagy or downregulation of autophagy-related genes -5 and -7 (ATG5 and ATG7, respectively). Autophagic flux was increased in TMZ-resistant P3 and T98G cells as indicated by diminished levels of the autophagy markers LC3A/B-II and increased STX17, higher protein degradation and no formation of p62 bodies nor induction of apoptosis. In contrast, BTZ treatment attenuated ULK1 mRNA, total and phosphorylated protein, and accumulated LC3A/B-II, p62 and autophagosomes analogously to Baf1 and chloroquine autophagy inhibitors. These autophagosomes did not fuse with lysosomes, indicated by attenuated STX17 expression and reduced degradation of long-lived proteins, which culminated in enhanced caspase-3/8 dependent apoptosis. BTZ synergistically enhanced TMZ efficacy, attenuated tumor cell proliferation, triggered ATM/Chk2 DNA damage signalling to further augment caspase-3/8 mediated apoptosis in the TMZ resistant P3 and T98G GBM cells. Genetic or chemical inhibition of autophagy (with CRISPR-CAs9 ATG5, ATG7 shRNA, MRT68921 or VPS34-IN1) abrogated BTZ efficacy and rescued BTZ+ TMZ treated GBM cells from death. We conclude that Bortezomib ameliorates temozolomide resistance through ATG5/7-dependent abrogated autophagic flux and may be amenable in combination treatment regimens for TMZ refractory GBM patients.
2023-03-10 | PXD021828 | Pride
Project description:LncRNA and mRNA expression data from TMZ-resistant cell line
| PRJNA821180 | ENA