Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dual inhibition of histone deacetylases and the mechanistic target of rapamycin promotes apoptosis in cell line models of uveal melanoma

ABSTRACT: Dual inhibition of histone deacetylases and the mechanistic target of rapamycin promotes apoptosis in cell line models of uveal melanoma

PROVIDER: PRJNA649782 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR12354765_1.fastq.gz	Fastqsanger.gz
	SRR12354765_2.fastq.gz	Fastqsanger.gz
	SRR12354766_1.fastq.gz	Fastqsanger.gz
	SRR12354766_2.fastq.gz	Fastqsanger.gz
	SRR12354767_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 24

Similar Datasets

Dual inhibition of histone deacetylases and the mechanistic target of rapamycin promotes apoptosis in cell line models of uveal melanoma

Project description:We investigated the effects of HDACi romidepsin and mTORi AZD-8055 in uveal melanoma cell line Mel202. Uveal melanomas harbor mutations in the GNAQ or GNA11 genes that activate survival pathways. As previous studies found that Ras-mutated cell lines were uniquely vulnerable to a combination of inhibitors of Ras-activated survival pathways and the histone-deacetylase inhibitor (HDI) romidepsin, we investigated whether this combination would be effective in models of uveal melanoma. A small-scale screen of inhibitors of bromodomain-containing protein 4 (BRD4, OTX-015), extracellular signal-related kinase (ERK, ulixertinib), mammalian target of rapamycin (mTOR, AZD-8055) or phosphoinositide 3-kinase (PI3K, GDC-0941) combined with a clinically-relevant administration of romidepsin was performed on a panel of uveal melanoma cell lines (92-1, Mel202, MP38, and MP41) and apoptosis was quantified by flow cytometry after 48 hr. RNA sequencing analysis was performed on Mel202 cells treated with romidepsin alone, the mTOR inhibitor AZD-8055 or the combination, and protein changes were validated by immunoblot. We found combining AZD-8055 with romidepsin was the most effective combination in inducing apoptosis in the cell lines. Increased caspase-3 and PARP cleavage were noted in the MP41 and Mel202 cell lines when they were treated with romidepsin and mTOR inhibitors. RNA sequence analysis of Mel202 cells revealed that apoptosis was the most affected pathway in the romidepsin/AZD-8055 treated cells. Increases in pro-apoptotic BCL2L11 and decreases in anti-apoptotic BIRC5 and BCL2L1 proteins noted in the sequencing analysis were confirmed at the protein level. Our data suggest that romidepsin in combination with mTOR inhibition could be an effective treatment strategy against uveal melanoma due in part to changes in apoptotic proteins.

2020-12-30 | GSE155452 | GEO

Dual Inhibition of Histone Deacetylases and the Mechanistic Target of Rapamycin Promotes Apoptosis in Cell Line Models of Uveal Melanoma.

Project description:PurposeOver 90% of uveal melanomas harbor pathogenic variants of the GNAQ or GNA11 genes that activate survival pathways. As previous studies found that Ras-mutated cell lines were vulnerable to a combination of survival pathway inhibitors and the histone-deacetylase inhibitor romidepsin, we investigated whether this combination would be effective in models of uveal melanoma.MethodsA small-scale screen of inhibitors of bromodomain-containing protein 4 (BRD4; OTX-015), extracellular signal-related kinase (ERK; ulixertinib), mechanistic target of rapamycin (mTOR; AZD-8055), or phosphoinositide 3-kinase (PI3K; GDC-0941) combined with a clinically relevant administration of romidepsin was performed on a panel of uveal melanoma cell lines (92.1, Mel202, MP38, and MP41) and apoptosis was quantified by flow cytometry after 48 hours. RNA sequencing analysis was performed on Mel202 cells treated with romidepsin alone, AZD-8055 alone, or the combination, and protein changes were validated by immunoblot.ResultsAZD-8055 with romidepsin was the most effective combination in inducing apoptosis in the cell lines. Increased caspase-3 and PARP cleavage were noted in the cell lines when they were treated with romidepsin and mTOR inhibitors. RNA sequencing analysis of Mel202 cells revealed that apoptosis was the most affected pathway in the romidepsin/AZD-8055-treated cells. Increases in pro-apoptotic BCL2L11 and decreases in anti-apoptotic BIRC5 and BCL2L1 transcripts noted in the sequencing analysis were confirmed at the protein level in Mel202 cells.ConclusionsOur data suggest that romidepsin in combination with mTOR inhibition could be an effective treatment strategy against uveal melanoma due in part to changes in apoptotic proteins.

| S-EPMC8458781 | biostudies-literature

Determination of protein level changes following inhibition of the mechanistic target of rapamycin

Project description:This study aimed to identify changes in protein level after inhibiting the mechanistic target of rapamycin using mass spectrometry analysis

2023-07-27 | PXD041933 | Pride

Rapamycin induced apoptosis when autophagy is inhibited

Project description:T-47 cells were treated with rapamycin, 3-methyladenine (3MA)-rapamycin and vehicle (DMSO, control) in a time series manner (1, 8, 24 and 48h), Affymetrix Genechip U133 Plus 2.0 array were used to compare the gene expression patterns of rapamycin-treated, 3MA-rapamycin treated versus control cells. All experiments were carried out in triplicates and a total of 24 chips were used. 3MA-Rapamycin treated samples were only limited to 24 h as total RNA for 48h was degraded.

2012-01-11 | E-MEXP-3487 | biostudies-arrayexpress

Mechanistic Target of Rapamycin Complex 2 (mTORC2) regulation of the primary human trophoblast cell transcriptome

Project description:Mechanistic Target of Rapamycin Complex 2 (mTORC2) regulation of the primary human trophoblast cell transcriptome

| PRJNA771456 | ENA

Karyotyping using SNP array of primary uveal melanoma cells, normal uveal melanocytes, neural crest stem cells, embryonic stem cells and uveal melanoma cell lines MUM2B and OCM1A

Project description:Karyotyping by SNP array of primary uveal melanoma samples, uveal melanoma cell lines and normal controls The Human660WQuad v1.0 DNA Analysis Bead Chip and kit were used for high resolution molecular karyotyping of DNA isolated from snap-frozen primary uveal melanoma tissue isolated from enucleated eyes.

2013-02-14 | E-GEOD-44297 | biostudies-arrayexpress

Epigenome analysis of primary uveal melanoma cells, normal uveal melanocytes, neural crest stem cells, embryonic stem cells and uveal melanoma cell lines

Project description:Genome wide DNA methylation profiling of primary uveal melanoma cells, normal uveal melanocytes, neural crest stem cells, embryonic stem cells and uveal melanoma cell lines. The Illumina Infinium 27k Human DNA methylation Beadchip Rev B was used to obtain DNA methylation profiles across approximately 27,000 CpGs in the samples. Samples included 58 primary UM, 3 NUM and NCSC controls and 2 cell lines. Bisulphite converted DNA from the 63 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip Rev B

2013-02-14 | E-GEOD-44296 | biostudies-arrayexpress

Effects of rapamycin, torin1, and rapalink1 on RNA levels

Project description:This study aimed to identify changes in RNA levels after inhibiting the mechanistic target of rapamycin using RNA sequencing.

2023-07-27 | GSE229623 | GEO

Epigenome analysis of primary uveal melanoma cells, normal uveal melanocytes, neural crest stem cells, embryonic stem cells and uveal melanoma cell lines

2013-02-14 | GSE44296 | GEO

Uveal melanoma cell lines and the primary tumors from which they are derived: comparison of their characteristics

Project description:Development of liver metastasis remains the most common cause of mortality in uveal melanoma (UM). Although advances in genomics allowed the direct evaluation of clinical samples of this eye cancer, there is still a need for reliable preclinical models to progress from correlative studies to mechanistic investigations. A few UM cell lines have been characterized, but so far the translation of basic knowledge to the clinic for the treatment of metastatic disease has been incremental at best. The aim of this study was to determine whether the properties of UM cell lines at various passages were similar to their corresponding primary tumors. Two primary uveal melanoma tumors and their derivative cell lines at three different passages are analyzed by gene profiling

2014-09-09 | E-GEOD-61228 | biostudies-arrayexpress

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