Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-29494
PROVIDER: PRJNA141657 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Mutations in the parkin gene, which encodes a ubiquitin ligase, are a major cause of autosomal recessive parkinsonism. Interestingly, parkin also plays a role in cancer as a putative tumor suppressor. Consistent with this, the gene is frequently targeted by deletion and inactivation in human malignant tumors. Here, we show that parkin expression is dramatically reduced in glioma cells, which correlates with increased cancer mortality. We further show that restoration of parkin expression in these cells promotes their arrest at G1 phase and significantly mitigates their proliferation rate both in vitro and in vivo. Notably, the level of cyclin D1, but not cyclin E, is reduced in parkin-expressing glioma cells. Moreover, parkin expression also leads to a selective downregulation of Akt serine-473 phosphorylation and VEGF receptor levels. Supporting this, cells derived from parkin null mouse exhibit increased levels of cyclin D1, VEGF receptor and Akt phosphorylation and divide significantly faster compared to their wild type counterparts. Importantly, analysis of parkin pathway activation revealed its predictive power for survival outcome of glioma patients. Taken together, our study provides a mechanism by which parkin exerts its tumor suppressor function and a signature pathway of parkin that is of potential prognostic value. Total RNA obtained from U-87MG cells stably expressing parkin or vector alone. Replicate arrays were performed for each of the 3 vector and parkin-expressing U-87MG clones.
2012-03-15 | E-GEOD-29494 | biostudies-arrayexpress
Project description:Mutations in the parkin gene, which encodes a ubiquitin ligase, are a major genetic cause of parkinsonism. Interestingly, parkin also plays a role in cancer as a putative tumor suppressor, and the gene is frequently targeted by deletion and inactivation in human malignant tumors. Here, we investigated a potential tumor suppressor role for parkin in gliomas. We found that parkin expression was dramatically reduced in glioma cells. Restoration of parkin expression promoted G1 phase cell cycle arrest and mitigated the proliferation rate of glioma cells in vitro and in vivo. Notably, parkin-expressing glioma cells showed a reduction in levels of cyclin D1, but not cyclin E, and a selective downregulation of Akt serine-473 phosphorylation and VEGF receptor levels. In accordance, cells derived from a parkin null mouse model exhibited increased levels of cyclin D1, VEGF receptor and Akt phosphorylation and divided significantly faster when compared with wild type cells, with suppressionof these changes following parkin re-introduction. Clinically, analysis of parkin pathway activation was predictive for the survival outcome of glioma patients. Taken together, our study provides mechanistic insight into the tumor suppressor function of parkin in brain tumors, and suggests that measurement of parkin pathway activation may be used clinically as a prognostic tool in brain tumor patients.
2012-03-15 | GSE29494 | GEO
Project description: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. we analyzed the expression and function of HOXD9 in human gliomas and found high expression of HOXD9 in GCSCs. HOXD9 contributes to cell proliferation and/or survival in glioma cells and glioma cancer stem-like cells.
2011-04-16 | E-GEOD-28618 | biostudies-arrayexpress
Project description:Ferroptosis-related Gene Signature Predicts Glioma Cell Death and Glioma Patient Progression
| PRJNA636819 | ENA
Project description:Cell surface sialylation confers many roles in cancer biology including cell proliferation, invasiveness, metastasis and angiogenesis. We show here that ST3Gal1 sialyltransferase marks a self-renewing cellular fraction. Depletion of ST3GAL1 abrogates glioma cell growth and tumorigenicity. In contrast, TGFb induces ST3GAL1 expression and correlates with the pattern of ST3Gal1 activation in patient tumors of the mesenchymal molecular subtype. To delineate the downstream events of ST3Gal1 signaling, we utilized a bioinformatical approach that leveraged on the greater statistical power of large patient databases, and subsequently verified our predictions in patient-derived glioma cells. We identify FoxM1, a major stem cell regulatory gene, as a downstream effector, and show that ST3Gal1 mediates the glioma phenotype through control of FoxM1 protein degradation Total RNA from primary neurosphere culture of brain tumor specimens non-treated and ST3GAL1 KD clones. The mRNAs of 5 unique glioma propagating cells (GPCs) were hybridized on Affymetrix HG-U133 Plus2 chips to study the transcriptomic impact of ST3GAL1 knock-down. Specimens were obtained from 5 glioma patients and replicate arrays were performed for all 5 neurosphere cultures.
2015-11-09 | E-GEOD-51395 | biostudies-arrayexpress
Project description:Genome-wide mRNA expression profiles of 200 primary gastric tumors from the Singapore patient cohort. Gastric cancer (GC) is the second leading cause of global cancer mortality, with individual gastric tumors displaying significant heterogeneity in their deregulation of various oncogenic pathways. We aim to identify major oncogenic pathways in GC that robustly impact patient survival and treatment response. We used an in silico strategy based on gene expression signatures and connectivity analytics to map patterns of oncogenic pathway activation in 25 unique GC cell lines, and in 301 primary gastric cancers from three independent patient cohorts. Of 11 oncogenic pathways previously implicated in GC, we identified three predominant pathways (proliferation/stem cell, NF-kB, and Wnt/b-catenin) deregulated in the majority (>70%) of gastric tumors. Using a variety of proliferative, Wnt, and NF-kB-related assays, we experimentally validated the pathway predictions in multiple GC cell lines showing similar pathway activation patterns in vitro. Patients stratified at the level of individual pathways did not exhibit consistent differences in clinical outcome. However, patients grouped by oncogenic pathway combinations demonstrated robust and significant survival differences (e.g., high proliferation/high NF-kB vs. low proliferation/low NF-kB), suggesting that tumor behavior in GC is likely influenced by the combined effects of multiple oncogenic pathways. Our results demonstrate that GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Experiment Overall Design: Profiling of 200 primary gastric tumors on Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. All tumors were collected with approvals from the National Cancer Centre, Singapore; the Research Ethics Review Committee; and signed patient informed consent.
2009-04-10 | E-GEOD-15459 | biostudies-arrayexpress
Project description:Protein Tyrosine Phosphatase Receptor Type N (PTPRN) plays an important role in diabetes and many cancers but its role in glioma remain poorly defined. Here, we firstly verified PTPRN expression was negatively correlated with overall survival of glioblastoma patients. Moreover, suppression of PTPRN expression reduced both U87 and U343 cell viability, suppressed proliferation, induced cell cycle arrest and inhibited glioma growth in vivo. Furthermore, KEGG and GO analysis demonstrated that PTPRN was involved in cell cycle signaling pathway, which were then confirmed by Western blot. In summary, we are the first to demonstrate that PTPRN inhibits glioma proliferation by targeting cell cycle signaling pathway. These data highlight PTPRN as a novel target for glioma treatment.
2020-01-14 | GSE143495 | GEO
Project description:While estrogen receptor positive breast tumors generally respond well to endocrine therapy (ET), up to 40% of patients will experience relapse, either while on endocrine therapy or after ET is completed. We have previously shown that the selective pressure of tamoxifen activates the pro-survival NFkB pathway in patient tumors, breast cancer cell lines, and breast cancer xenograft tumors, and that this activation allows for survival of a population of ET-tolerant cells, which can contribute to relapse after ET withdrawal. Here, we utilized single cell RNA-sequencing to characterize survival pathways in NFkB+, ET-tolerant cells and identified activation of the integrated stress response as a critical survival mechanism. Moreover, we found key players in this pathway are regulated by ET in patient derived organoids. In addition, we developed an ET-tolerant gene signature that can be found in metastatic cell populations and that predicts poor outcome to ET. Our findings suggest that co-targeting of ER and key players in the integrated stress response may be a viable therapeutic strategy to eliminate cells that survive the selective pressure of ET.
2022-03-15 | GSE181812 | GEO
Project description:Genome-wide mRNA expression profiles of 31 primary gastric tumors from the UK patient cohort. Gastric cancer (GC) is the second leading cause of global cancer mortality, with individual gastric tumors displaying significant heterogeneity in their deregulation of various oncogenic pathways. We aim to identify major oncogenic pathways in GC that robustly impact patient survival and treatment response. We used an in silico strategy based on gene expression signatures and connectivity analytics to map patterns of oncogenic pathway activation in 25 unique GC cell lines, and in 301 primary gastric cancers from three independent patient cohorts. Of 11 oncogenic pathways previously implicated in GC, we identified three predominant pathways (proliferation/stem cell, NF-kB, and Wnt/b-catenin) deregulated in the majority (>70%) of gastric tumors. Using a variety of proliferative, Wnt, and NF-kB-related assays, we experimentally validated the pathway predictions in multiple GC cell lines showing similar pathway activation patterns in vitro. Patients stratified at the level of individual pathways did not exhibit consistent differences in clinical outcome. However, patients grouped by oncogenic pathway combinations demonstrated robust and significant survival differences (e.g., high proliferation/high NF-kB vs. low proliferation/low NF-kB), suggesting that tumor behavior in GC is likely influenced by the combined effects of multiple oncogenic pathways. Our results demonstrate that GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Experiment Overall Design: Profiling of 31 primary gastric tumors on Affymetrix GeneChip Human Genome U133 Array Set HG-U133A. All tumors were collected with approvals from the St James's University Hospital, United Kingdom and the Research Ethics Review Committee.
2009-04-10 | E-GEOD-15456 | biostudies-arrayexpress
Project description:Genome-wide mRNA expression profiles of 25 unique gastric cancer cell lines (GCCLs). Gastric cancer (GC) is the second leading cause of global cancer mortality, with individual gastric tumors displaying significant heterogeneity in their deregulation of various oncogenic pathways. We aim to identify major oncogenic pathways in GC that robustly impact patient survival and treatment response. We used an in silico strategy based on gene expression signatures and connectivity analytics to map patterns of oncogenic pathway activation in 25 unique GCCLs, and in 301 primary gastric cancers from three independent patient cohorts. Of 11 oncogenic pathways previously implicated in GC, we identified three predominant pathways (proliferation/stem cell, NF-kB, and Wnt/b-catenin) deregulated in the majority (>70%) of gastric tumors. Using a variety of proliferative, Wnt, and NF-kB-related assays, we experimentally validated the pathway predictions in multiple GC cell lines showing similar pathway activation patterns in vitro. Patients stratified at the level of individual pathways did not exhibit consistent differences in clinical outcome. However, patients grouped by oncogenic pathway combinations demonstrated robust and significant survival differences (e.g., high proliferation/high NF-kB vs. low proliferation/low NF-kB), suggesting that tumor behavior in GC is likely influenced by the combined effects of multiple oncogenic pathways. Our results demonstrate that GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Keywords: gastric cancer, cell culture Profiling of 25 unique Gastric Cancer Cell Lines on Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. Replicates are included for a total of 33 arrays.
2009-10-06 | E-GEOD-15455 | biostudies-arrayexpress