Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bulk RNA-sequencing results of p16INK4A-high and -low glioblastoma, IDH-wild type, grade 4.

ABSTRACT: The expression of p16INK4A is widely used to identify fully senescent cells in noncancerous tissues, as well as senescent cancer cells in various types of cancer. In our study, we observed diffuse expression of p16INK4A in around 40 % of the patients with wild-type CDKN2A gene without mutation showing senescence phenotype, correlating with significant differences in overall survival between patients with high and low levels of p16INK4A expression. This prognostic distinction led us to hypothesize that cellular senescence in glioblastoma cells might confer a favorable effect on patient outcomes. To investigate the mechanism underlying this phenotype, we conducted RNA sequencing on 11 samples of glioblastoma, IDH-wild type along with corresponding in vivo and in vitro studies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE266210 | GEO | 2024/05/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A Dual Role of the Senescence Marker P16Ink4a in Liver Endothelial Cell Function

Project description:P16Ink4a is a well-established marker of senescence. Although P16Ink4a is expressed in endothelial cells, little is known about its function in these cells. Using isolated liver endothelial cells with silencing or overexpression of P16Ink4a, we show here that dependent on P16Ink4a levels, different pathways and functions are affected. High levels of P16Ink4a reduce proliferation and induce senescence while low levels have the opposite effects. Only high P16Ink4a expression reduces in vitro angiogenesis. Expression profiling reveals an inflammatory phenotype upon silencing of P16Ink4a while P16Ink4a overexpression is associated with a profile associated to DNA damage, repair and senescence. Low levels of P16Ink4a induce reactive oxygen species (ROS) generation and increase endothelial cell leakage. Collectively, P16Ink4a represents an “antagonistic pleiotropy” gene, which is on the one hand required to prevent ROS generation and endothelial damage and on the other hand at high levels inhibits angiogenesis through induction of senescence.

2024-11-18 | GSE281665 | GEO

ADAR1 downregulation contributes to p16INK4a upregulation independent of RNA editing during senescence

Project description:Cellular senescence plays a causal role in ageing and, in mouse, depletion of p16INK4a-expressing senescent cells delays ageing-associated disorders. Adenosine deaminases acting on RNA (ADARs) RNA editing enzymes are also implicated as important regulators of human ageing and ADAR inactivation causes age-associated pathologies such as neurodegeneration in model organisms. However, the role, if any, of ADARs in cellular senescence is unknown. Here we show that ADAR1 is post-transcriptionally downregulated by autophagic degradation to promote senescence through upregulating p16INK4a. ADAR1 is downregulated during senescence post-transcriptionally by autophagy-lysosomal pathway and the downregulation is sufficient to drive senescence in both in vitro and in vivo models. Senescence induced by ADAR1 downregulation is p16INK4a dependent and independent of its RNA editing function. Mechanistically, ADAR1 promotes SIRT1 expression by affecting its RNA stability through HuR, an RNA binding protein that increases the half-life and steady state levels of its target mRNAs. And SIRT1, in turn, antagonizes translation of mRNA encoding p16INK4a. Hence, downregulation of ADAR1 and SIRT1 mediates p16INK4aupregulation by enhancing its mRNA translation. Finally, Adar1 is downregulated during ageing of mouse tissues such as brain, ovary, and intestine, and Adar1 expression correlates with Sirt1 expression in these tissues in mice. Together, our study reveals an RNA-editing independent role of ADAR1 in regulating senescence by post-transcriptionally controlling p16INK4a expression.

2022-04-25 | GSE179423 | GEO

Bulk RNA-sequencing results of p16INK4A-high and -low glioblastoma, IDH-wild type, grade 4.

Project description:Bulk RNA-sequencing results of p16INK4A-high and -low glioblastoma, IDH-wild type, grade 4.

| PRJNA1106382 | ENA

Safety and Efficacy of NEO212 in Patients With Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype or Brain Metastasis

Project description:This multi-site, Phase 1/2 clinical trial is an open-label study to identify the safety, pharmacokinetics, and efficacy of a repeated dose regimen of NEO212 for the treatment of patients with radiographically-confirmed progression of Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype, and the safety, pharmacokinetics and efficacy of a repeated dose regimen of NEO212 when given with select SOC for the treatment of solid tumor patients with radiographically confirmed uncontrolled brain metastasis. The study will have three phases, Phase 1, Phase 2a and Phase 2b.

| 92735 | ecrin-mdr-crc

Sentinel p16INK4a+ cells in the basement membrane form a reparative niche in the lung [RNA-Seq]

Project description:We collected freshly sorted mesenchyme (live CD45-Epcam-CD31-PDGFRa+GFP- or GFP+) from dissociated lung tissue of INKBRITE animals to characterize the transcriptome difference between p16INK4a+ vs p16INK4a- cells at homeostasis and during injury. We used fluorescence activated cell sorting (FACS) to exclude immune (CD45+), epithelial (Epcam+), and endothelial (CD31+) cells and positively select for PDGFRa+ mesenchyme. Cells were sequenced at a depth of average of 45 million reads/sample. The results revealed an increase of senescence associated secretory phenotype (SASP) signature in p16INK4+ cells that becomes refined after injury. We found the expression of an epithelial growth factor epiregulin (ereg) increased in p16INK4a+ cells after injury suggesting a possible role of p16INK4a+ senescence during regeneration of lung epithelium.

2022-11-02 | GSE140654 | GEO

Post-GWAS functional analysis identifies CUX1 as a regulator of p16INK4a and cellular senescence

Project description:Accumulation of senescent cells with age is believed to be an important driver of aging and age-related diseases. However, the underlying mechanisms and the signaling pathways that regulate senescence remain elusive. In this report, we couple high throughput (HTP) mapping of disease-associated functional SNPs (fSNPs) with proteomics analysis of fSNP-binding regulatory proteins to dissect the CDKN2A/B locus, a locus known to be associated with multiple age-related diseases, as well as overall human longevity. We demonstrate that the homeodomain transcription factor CUX1 specifically binds to a fSNP (rs1537371) associated with atherosclerosis within the CDKN2A/B locus. Although it binds at a considerable distance (> 100 kb), CUX1 is shown to regulate the CDKN2A/B encoded genes p14ARF, p15INK4b, p16INK4a, and ANRIL in endothelial cells (ECs). In-depth analysis demonstrates that endothelial CUX1 expression correlates with telomeric length and is induced by both DNA-damaging agents and oxidative stress. Moreover, induction of CUX1 expression triggers both replicative and stress-induced premature senescence via activating p16INK4A expression. Consistent with these findings, we also detect elevated expression of CUX1 and p16INK4A in the plaques of patients with carotid artery disease. Our HTP strategy therefore identifies CUX1 as a regulator of p16INK4A expression and endothelial senescence and a potential therapeutic target for atherosclerosis and other age-related diseases.

2021-12-05 | GSE186528 | GEO

Cysteine oxidation triggers amyloid fibril formation of the tumor suppressor p16INK4A

Project description:p16INK4A inhibits the CDK4/6 kinases and is therefore an important cell cycle regulator. Accumulation of p16INK4A in response to oncogenic transformation leads to cellular senescence and it is therefore frequently lost in cancer. p16INK4A is also known to accumulate under conditions of cellular oxidative stress and therefore could potentially be regulated by redox signaling, which is a form of signal transduction that is mediated by the reversible oxidation of cysteine-thiol side chains in proteins. We found that oxidation of the single cysteine residue in p16INK4A in human cells occurs under relatively mild oxidizing conditions and that this leads to disulfide dependent dimerization. p16INK4A is a well-characterized all alpha-helical protein, but we find that upon cysteine-dependent dimerization, p16INK4A undergoes a dramatic structural rearrangement and forms aggregates that have the typical features of amyloid fibrils, including binding of diagnostic dyes, presence of cross-β sheet structure, and typical dimensions found in electron microscopy. We find that p16INK4A amyloid formation abolishes its function as a CDK4/6 inhibitor in human cells. Taken together, these observations mechanistically link the cellular redox state to the inactivation of p16INK4A through the formation of amyloid fibrils.

2019-09-04 | PXD012353 | Pride

REST transcription factor holds the balance between the invasion and cell differentiation in IDH-mutant and IDH-wild type gliomas

Project description:Glioblastoma is the deadliest brain tumor with median survival of 15 months due to diffusive growth and lack of efficient therapy. Recurrent mutations in genes coding for isocitrate dehydrogenases (IDH) 1 or 2 cause to a change in function of the enzymes, resulting in production of 2-hydroxyglutarate, which leads to DNA hypermethylation phenotype, affecting transcription activators/repressors binding to DNA and gene expression. REST is a canonical repressor of neuronal genes in non-neuronal cells, whose levels differ between IDH wt and mut gliomas and whose expression levels correlate with the patients’ survival probability.

2022-04-15 | GSE174308 | GEO

Mutant IDH modulates suppressive myeloid populations in malignant glioma

Project description:RNA-sequencing for myeloid inflammation-related genes was conducted on primary tumor samples from patients with IDH-wildtype glioblastoma (GBM) and grade 4 IDH-mutant astrocytoma (G4IMA). In addition, the IDH-wildtype murine glioma cell line GL261 and a strain of IDH-mutant GL261 were also sequenced using the murine counterpart of the RNA-sequencing myeloid innate immunity panel.

2024-05-29 | GSE268118 | GEO

Cellular senescence in malignant cells promotes tumorigenesis in mouse and patient glioblastoma [10X scRNA-seq]

Project description:The goal of this study is to identify the senescent cells expressing high level of p16Ink4a (p16Ink4a Hi) in GBMs, at an early timepoint. We introduced the p16-3MR transgene in the GBM mouse model to selectively delete p16Ink4a Hi senescent cells upon ganciclovir (GCV) injection. We compared two p16-3MR+GCV to two WT+GCV control GBMs that were harvested 7 days after the last GCV injection. p16Ink4a Hi senescent cells were a subset of malignant cells, mostly grouped in the astrocyte cluster and to a lesser extend in the NP-like cluster. We also found that p16Ink4a Hi senescent cells deletion modifies the cell state of malignant cells and modulates the tumor microenvironment. This study allowed us to define a GBM senescence signature.

2022-12-15 | GSE168038 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data