Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-seq analysis in uveal melanoma cells 92.1 and OMM1

ABSTRACT: The goals of this study are to compare gene expression profiles between uveal melanoma cells treated with either a scrambled antisense oligonucleotide (NTC) or a SAMMSON inhibiting ASO wether or not in combination with mTOR inhibitor GDC-0349. GDC-0349 synergizes with SAMMSON ASO to further reduce cell viability. Based on the RNA seq data, we observed only a limited number of DEGs in the GDC-0349 treated cells, while the number of DEGs in the combination significantly increased compared to SAMMSON ASO alone with many overlapping genes showing a more pronounced log2foldchange.

ORGANISM(S): Homo sapiens

PROVIDER: GSE184685 | GEO | 2022/09/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

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

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

LKB1-SIK2 loss drives uveal melanoma proliferation and hypersensitivity to SLC8A1 and ROS inhibition

Project description:Metastatic uveal melanomas are highly resistant to all existing treatments. To address this critical issue, we performed a genome-wide CRISPR-Cas9 knockout screen, which revealed the LKB1-SIK2 module in restraining uveal melanoma tumorigenesis. Functionally, LKB1 loss enhances proliferation and survival through SIK2 inhibition and up-regulation of the sodium/calcium (Na+/Ca2+) exchanger SLC8A1. This signalling cascade promotes increased level of intracellular calcium and mitochondrial reactive oxygen species, two hallmarks of cancer. We further demonstrate that combination of an SLC8A1 inhibitor and a mitochondria-targeted antioxidant promotes enhanced cell death efficacy in LKB1- and SIK2-negative uveal melanoma cells compared to control cells. We also designed an LKB1-deficient prognostic gene signature of patient survival that may be predictive of response to this combination. Our data thus identify not only metabolic vulnerabilities, but also new prognostic markers, thereby providing a therapeutic strategy for particular subtypes of metastatic uveal melanoma.

2024-05-25 | GSE233458 | GEO

Combined Inhibition of Gaq and MEK Enhances Therapeutic Efficacy in Uveal Melanoma

Project description:We developed an isogenic melanocytic cellular system and systematically examined the hotspot mutations in GNAQ (e.g., G48V, R183Q, Q209L) and CYSLTR2 (e.g. L129Q) in human uveal melanoma. Biochemical and cell viability assays validated YM-254890 as a potent inhibitor of cell signaling and growth. Human uveal melanoma cells and mouse models recapitulated this finding, indicating that YM is also effective in vivo. Combination of YM and MEK inhibition leads to further decreases in MAPK pathway gene expression and cell viability. Furthermore, our cellular and mouse models show that combination leads to long term signaling inhibition and significant decreases in tumor burden.

2020-12-31 | GSE160112 | GEO

Combined Inhibition of Gaq and MEK Enhances Therapeutic Efficacy in Uveal Melanoma.

2020-12-31 | GSE152705 | 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

Genome-wide gene expression analysis 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:Gene expression in primary uveal melanoma cells and normal cell controls The HumanHT-12 v3 gene expression microarray (Illumina) was used to analyze RNA isolated from snap-frozen primary uveal melanoma tissue isolated from enucleated eyes and from normal cell controls.

2013-02-14 | E-GEOD-44295 | biostudies-arrayexpress

HDAC inhibition enhances the in vivo efficacy of MEK inhibitor therapy in uveal melanoma

Project description:Purpose: The clinical use of MEK inhibitors in uveal melanoma is limited by the rapid acquisition of resistance. The current study has used multi-omics approaches and drug screens to identify the pan-HDAC inhibitor panobinostat as an effective strategy to limit MEK inhibitor resistance. Experimental Design: Mass spectrometry-based proteomics and RNA-Seq was used to identify the signaling pathways involved in the escape of uveal melanoma cells from MEK inhibitor therapy. Mechanistic studies were performed to evaluate the escape pathways identified and the efficacy of the MEK-HDAC inhibitor combination was demonstrated in multiple in vivo xenograft models of uveal melanoma. Results: We identified a number of putative escape pathways that were upregulated following MEK inhibition including the PI3K/AKT pathway, ROR1/2 and IGF1R signaling. MEK inhibition was also associated with a widespread increase in GPCR expression, particularly the Endothelin B receptor and that this contributed to therapeutic escape through YAP signaling. A screen of 289 clinical grade compounds identified HDAC inhibitors as potential candidates that suppressed the adaptive YAP and AKT signaling that followed MEK inhibition. In vivo xenograft studies revealed the MEK-HDAC inhibitor combination to outperform either agent alone, leading to a long-term decrease of tumor growth and the suppression of adaptive PI3K/AKT and YAP signaling. Conclusions Together our studies have identified GPCR-mediated YAP activation and RTK-driven AKT signaling as key pathways involved in the escape of uveal melanoma cells from MEK inhibition. We further demonstrate that HDAC inhibition is a promising combination partner for MEK inhibitors in uveal melanoma.

2020-05-26 | PXD013988 | Pride