Identifying RBBP4-regulated transcriptome in T98G glioblastoma (GBM) cells using RNA sequencing, and epigenome screening for genes regulated by RBBP4 in GBM cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE72477 | GEO | 2016/08/27
SECONDARY ACCESSION(S): PRJNA294116
REPOSITORIES: GEO
Similar Datasets
Project description:Identifying RBBP4-regulated transcriptome in T98G glioblastoma (GBM) cells using RNA sequencing, and epigenome screening for genes regulated by RBBP4 in GBM cells
| PRJNA294116 | ENA
Project description:Retinoblastoma-binding protein 4 (RBBP4) is a chromatin modifying protein regulating multiple cellular functions. We have identified RBBP4 as a critical modulator of therapy response in glioblastoma (GBM). The purpose of this study was to identify genes through which RBBP4 regulates this important role with expectation of identifying candidates for therapy sensitizing strategy in GBM, and perhaps in other human malignancies.
2016-08-27 | GSE72475 | GEO
Project description:We report that RBBP4 has dual effect on gene regulation, whereby some genes are downregulated (~60%) while others are activated (~40%).
2016-08-27 | GSE72476 | GEO
Project description:: Glioblastoma multiforme (GBM) is the most malignant form of primary brain tumour with extremely poor prognosis. The current standard of care for newly diagnosed GBM includes maximal surgical resection followed by radiotherapy and adjuvant chemotherapy. The introduction of this protocol has improved overall survival, however recurrence is essentially inevitable. The key reason for that is that the surgical treatment fails to eradicate GBM cells completely, and adjacent parenchyma remains infiltrated by scattered GBM cells which become the source of recurrence. This stimulates interest to any supplementary methods which could help to destroy residual GBM cells and fight the infiltration. Photodynamic therapy (PDT) relies on photo-toxic effects induced by specific molecules (photosensitisers) upon absorption of photons from a light source. Such toxic effects are not specific to a particular molecular fingerprint of GBM, but rather depend on selective accumulation of the photosensitiser inside tumour cells or, perhaps their greater sensitivity to the effects, triggered by light. This gives hope that it might be possible to preferentially damage infiltrating GBM cells within the areas which cannot be surgically removed and further improve the chances of survival if an efficient photosensitiser and hardware for light delivery into the brain tissue are developed. So far, clinical trials with PDT were performed with one specific type of photosensitiser, protoporphyrin IX, which tends to accumulate in the cytoplasm of the GBM cells. In this review we discuss the idea that other types of molecules which build up in mitochondria could be explored as photosensitisers and used for PDT of these aggressive brain tumours.
| S-EPMC7071600 | biostudies-literature
Project description:The WWOX gene is known for its tumor suppressor character and seems to be one of the main cellular regulators of cell cycle and apoptosis. The aim of the study was to identify cellular pathways and biological processes influenced by WWOX in glioblastoma cells. Our experiment showed that in this type of cancer WWOX, beside cell cycle and apoptosis control, may be involved in metabolism, cytoskeleton structure and differentiation. T98G glioblastoma cells were stably transfected with WWOX cDNA. T98G cells transfected with an empty vector served as a control. Total mRNA was isolated to look for gene-expression differences induced by the WWOX overexpression.
| S-ECPF-GEOD-51481 | biostudies-other
Project description:Z-ligustilide (LIG), an essential oil extract from Radix Angelica sinensis, has broad pharmaceutical applications in treating cardio-vascular diseases and ischemic brain injury. Recently, LIG has been connected to Glioblastoma multiforme (GBM) because of its structural similarity to 3-n-alkyphthalide (NBP), which is specifically cytotoxic to GBM cells. Hence, we investigated LIG's effect on GBM T98G cells. The study shows that LIG can significantly reduce T98G cells' migration in a dose-dependent manner. Furthermore, the attenuation of cellular mobility can be linked to the activity of the Rho GTPases (RhoA, Rac1 and Cdc42), the three critical molecular switches governing cytoskeleton remodeling; thus, regulating cell migration. LIG significantly reduces the expression of RhoA and affects in a milder manner the expression of Cdc42 and Rac1.
| S-EPMC3689746 | biostudies-literature
Project description:Protein trafficking is altered when normal cells acquire a tumor phenotype. A key subcellular compartment in regulating protein trafficking is the Golgi apparatus, but its role in carcinogenesis is still not well defined. Golgi phosphoprotein 3 (GOLPH3), a peripheral membrane protein mostly localized at the trans-Golgi network, is overexpressed in several tumor types including glioblastoma multiforme (GBM), the most lethal primary brain tumor. Moreover, GOLPH3 is currently considered an oncoprotein, however its precise function in GBM is not fully understood. Here, we analyzed in T98G cells of GBM, which express high levels of epidermal growth factor receptor (EGFR), the effect of stable RNAi-mediated knockdown of GOLPH3. We found that silencing GOLPH3 caused a significant reduction in the proliferation of T98G cells and an unexpected increase in total EGFR levels, even at the cell surface, which was however less prone to ligand-induced autophosphorylation. Furthermore, silencing GOLPH3 decreased EGFR sialylation and fucosylation, which correlated with delayed ligand-induced EGFR downregulation and its accumulation at endo-lysosomal compartments. Finally, we found that EGF failed at promoting EGFR ubiquitylation when the levels of GOLPH3 were reduced. Altogether, our results show that GOLPH3 in T98G cells regulates the endocytic trafficking and activation of EGFR likely by affecting its extent of glycosylation and ubiquitylation.
| S-EPMC7700535 | biostudies-literature
Project description: Not available
| S-EPMC6909277 | biostudies-literature
Project description:We have recently shown that replication forks pause near origins in normal human fibroblasts (NHF1-hTERT) but not glioblastoma T98G cells. This observation led us to question whether other differences in the replication program may exist between these cell types that may relate to their genetic integrity. To identify differences, we detected immunoflourescently the sequential incorporation of the nucleotide analogs IdU and CldU into replicating DNA at the start of every hour of a synchronized S phase. We then characterized the patterns of labeled replicating DNA tracks and quantified the percentages and lengths of the tracks found at these hourly intervals. From the directionality of labeling in single extended replicating DNA fibers, tracks were categorized as single bidirectional origins, unidirectional elongations, clusters of origins firing in tandem, or merging forks (terminations). Our analysis showed that the start of S phase is enriched in single bidirectional origins in NHF1-hTERT cells, followed by an increase in clustering during mid S phase and an increase in merging forks during late S phase. Early S phase in T98G cells also largely consisted of single bidirectional origin initiations; however, an increase in clustering was delayed until an hour later, and clusters were shorter in mid/late S phase than in NHF1-hTERT cells. The spike in merging forks also did not occur until an hour later in T98G cells. Our observations suggest models to explain the temporal replication of single and clustered origins, and suggest differences in the replication program in a normal and cancer cell line.
| S-EPMC2829940 | biostudies-literature
Project description:Glioblastoma multiforme (GBM) is the most aggressive type of malignant brain tumor. Current FDA-approved treatments include surgical resection, radiation, and chemotherapy, while hyperthermia, immunotherapy, and most relevantly, nanoparticle (NP)-mediated delivery systems or combinations thereof have shown promise in preclinical studies. Drug-carrying NPs are a promising approach to brain delivery as a result of their potential to facilitate the crossing of the blood-brain barrier (BBB) via two main types of transcytosis mechanisms: adsorptive-mediated transcytosis (AMT) and receptor-mediated transcytosis (RMT). Their ability to accumulate in the brain can thus provide local sustained release of tumoricidal drugs at or near the site of GBM tumors. NP-based drug delivery has the potential to significantly reduce drug-related toxicity, increase specificity, and consequently improve the lifespan and quality of life of patients with GBM. Due to significant advances in the understanding of the molecular etiology and pathology of GBM, the efficacy of drugs loaded into vectors targeting this disease has increased in both preclinical and clinical settings. Multitargeting NPs, such as those incorporating multiple specific targeting ligands, are an innovative technology that can lead to decreased off-target effects while simultaneously having increased accumulation and action specifically at the tumor site. Targeting ligands can include antibodies, or fragments thereof, and peptides or small molecules, which can result in a more controlled drug delivery system compared to conventional drug treatments. This review focuses on GBM treatment strategies, summarizing current options and providing a detailed account of preclinical findings with prospective NP-based approaches aimed at improving tumor targeting and enhancing therapeutic outcomes for GBM patients.
| S-EPMC8092804 | biostudies-literature