Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

13 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional profiles of NRAS- and BRAF-mutant melanoma cell lines under normal conditions and in response to glucose starvation

ABSTRACT: NRAS and BRAF are the most commonly found genetic alterations in melanoma. It has been demonstrated that NRAS and BRAF oncogenic alterations, even affecting the same signaling pathway, represent two different clinical and biochemical entities, showing different signaling patterns and biological responses. Metabolic reprogramming is considered a novel target to control cancer; however, it is mostly unknown how the NRAS oncogene contributes to this cancer hallmark. We have showed that NRAS-mutated melanomas harbor specific metabolic alterations that render cells sensitive to RAS pathway inhibition upon metabolic stress. Gene expression analysis has confirmed different transcriptional profiles of NRAS- and BRAF- mutant cells both, under basal conditions and in response to glucose starvation. Moreover, analysis of glucose metabolism-related genes expression regulation revealed PFKFB2 as an important player linking glycolysis and RAS pathway activation.

ORGANISM(S): Homo sapiens

SUBMITTER: Juan Ángel Recio Conde

PROVIDER: E-MTAB-10921 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

miR-146a promotes the initiation and progression of melanoma by activating Notch signaling

Project description:Oncogenic mutations in BRAF and NRAS occur in 70% of melanomas. Here we identify a microRNA, miR-146a, that is highly upregulated by oncogenic BRAF and NRAS. Expression of miR-146a increases the ability of human melanoma cells to proliferate in culture and form tumors in mice, whereas knockdown of miR-146a has the opposite effects. We show these oncogenic activities are due to miR-146a targeting the NUMB mRNA, a repressor of Notch signaling. Previous studies have shown that pre-miR-146a contains a single nucleotide polymorphism (C>G rs2910164). We find that the ability of pre-miR-146a/G to activate Notch signaling and promote oncogenesis is substantially higher than that of pre-miR-146a/C. Analysis of melanoma cell lines and matched patient samples indicates that during melanoma progression pre-miR-146a/G is enriched relative to pre-miR-146a/C, resulting from a C-to-G somatic mutation in pre-miR-146a/C. Collectively, our results reveal a central role for miR-146a in the initiation and progression of melanoma. SKMEL28 melanoma cell line stably expressing either an empty vector or pre-miR146a with either C or G SNP (SKMEL28-FG12, SKMEL28-miR-146a/C and SKMEL28-miR-146a/G) were used to prepare total RNA. Microarray analysis was performed by using biological replicates for each stable cell lines for a total of 6 samples.

2014-02-18 | E-GEOD-39294 | biostudies-arrayexpress

BRAF activation by metabolic stress promotes glycolysis and survival, sensitizing NRASQ61 mutated melanomas to targeted therapy.

Project description:NRAS-mutated melanoma lacks an approved first-line treatment. Metabolic reprogramming is considered a novel target to control cancer; however, it is mostly unknow how the NRAS oncogene contributes to this cancer hallmark. Here, we show that NRASQ61-mutated melanomas harbor specific metabolic alterations that render cells sensitive to sorafenib upon metabolic stress. Mechanistically, these cells seem to depend on glucose metabolism, as glucose deprivation promotes the switch of the RAF isoform used from CRAF to BRAF. This process contributes to cell survival and sustains glucose metabolism through the phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2/6- phosphofructo-2-kinase/fructose-2,6-bisphosph 3 (PFKFB2/PFKFB3) heterodimers by BRAF. In turn, this phosphorylation favors the allosteric activation of phosphofructokinase-1 (PFK1), generating a feedback loop linking glycolysis and the RAS signaling pathway. In vivo treatment of NRASQ61 mutant melanomas, including patient-derived xenografts, with the combination of 2-deoxy-D-glucose (2-DG) and sorafenib effectively inhibits tumor growth. Thus, we provide evidence of the contributions of NRAS oncogenes to metabolic rewiring and proof of principle for the treatment of NRAS-mutated melanoma with combinations of metabolic stress (glycolysis inhibitors) and already approved drugs such as sorafenib.

2023-01-09 | PXD028297 | Pride

Genetic dynamics in untreated chronic lymphocytic leukemia patients with either stable or progressive disease: a longitudinal study.

Project description:We investigated at two time points a longitudinal cohort of 27 untreated Chronic Lymphocytic Leukemia (CLL) patients with either stable or progressive disease. The sequenced genes included BCOR, EGR2, HIST1H1E, ITPKB, KRAS, MED12, NRAS, RIPK1, SAMHD1, ATM, BIRC3, BRAF, CHD2, DDX3X, DDX3Y, FBXW7, KIT, KLHL6, MAPK1, MYD88, NOTCH1, PIK3CA, POT1, SF3B1, TP53, XPO1 and ZMYM3, which were previously identified as mutated in CLL studies.

2019-11-05 | E-MTAB-8020 | biostudies-arrayexpress

Whole-exome sequencing of genomic DNA extracted from patient-derived melanoma cell lines resistant to vemurafenib (PLX).

Project description:Whole-exome sequencing was performed on DNA sample extracted from one melanoma cell line resistant to vemurafenib (BRAF V600E inhibitor). The aim of the experiment was to search for genetic alterations responsible for phenotypic diversity of melanoma cell lines reported at the level of cell morphology, activity of signaling pathways essential for melanoma development and progression, and resistance to targeted therapeutics.

2019-07-25 | E-MTAB-8150 | biostudies-arrayexpress

Whole-exome sequencing of genomic DNA extracted from patient-derived melanoma cell lines resistant to vemurafenib (PLX) or trametinib (TRA)

Project description:Whole-exome sequencing was performed on DNA samples extracted from seven melanoma cell lines resistant to either vemurafenib (BRAF V600E inhibitor) or trametinib (MEK1/2 inhibitor). The aim of the experiment was to search for genetic alterations responsible for phenotypic diversity of melanoma cell lines reported at the level of cell morphology, activity of signaling pathways essential for melanoma development and progression, and resistance to targeted therapeutics.

2018-10-20 | E-MTAB-7248 | biostudies-arrayexpress

Whole-exome sequencing of genomic DNA from patient-derived melanoma cell lines resistant to either vemurafenib (PLX) or trametinib (TRA).

2019-06-15 | E-MTAB-7991 | biostudies-arrayexpress

RNA seq of human fibroblasts treated with Rocuronium bromide

Project description:Cancer associated fibroblasts (CAFs) as the main stromal cells in tumor microenvironment can provide metabolic links with tumor cells through metabolic derivatives such as cytokines released, creating a favorable metabolic microenvironment for tumor progression. Recent in vitro and in vivo studies have discovered that anesthetics can affect tumor malignancy. However, the mechanism is unknown, and the total-body dosage and short-term treatment duration of anesthetic drugs are still far from tumor treatment. Now, our study focuses on the effect of rocuronium bromide (RB) on CAFs. In order to restore the true effects of CAFs by RB, we studied the global transcriptomic signatures of human fibroblasts derived from different tissues (skin HS-27; lung TIG-1; dermal CRL-7815) by 160 μg/mL RB to find the target genes responding to RB.

2022-05-22 | E-MTAB-11728 | biostudies-arrayexpress

RNA sequencing analysis of Nras mutant MEFs

Project description:Purpose: Emerging evidence in the field of RAS biology is beginning to illustrate that RAS mutations are functionally distinct. To elucidate functional differences between NRAS mutants we performed RNA-sequencing on mouse embryonic fibroblasts (MEFs) expressing different NRAS codon 61 variants from the endogenous gene locus Methods: MEFs were isolated from Tyr::CRE-ERT2 LSL-Nras mouse models containing different Nras variants in the endogeous gene locus. NRAS expression was induced in MEFs using an Adenoviral Cre delivery system. RNA was isolated from MEFs six days post-NRAS induction and submitted for RNA-sequencing Results: Differential expression and gene set enrichment analysis (GSEA) between NRAS variants revealed enrichment of transcripts associated with cellular proliferation between all mutant Nras alleles versus wild-type Nras. Further, MEFs expressing NRAS mutants capable of driving melanoma formation were enriched for transcripts associated with RAS-MYC signaling axis. Conclusion: While all NRAS mutants are capable of enhancing cellular proliferation versus wild-type NRAS, the melanomagenic potential of these mutants correlates with the ability to enhance activation of the RAS-MYC signaling axis

2022-04-30 | GSE162124 | GEO

Targeted inhibition of ubiquitin signaling reverses the metabolic reprogramming and suppresses Glioblastoma growth

Project description:Glioblastoma (GBM) is the most frequent and aggressive form of primary brain tumor in the adult population, and the high recurrence rate and resistance to current therapeutics urgently demand a better therapy for this disease. Regulation of protein stability by the ubiquitin proteasome system (UPS) represents an important control mechanism of cell growth. Deregulation of UPS is mechanistically linked to the development and progression of a variety of human cancers, including GBM. Thus, UPS system represents a valuable target for GBM treatment. Here, we find that the E3 ligase praja2 selectively marks primary IDH1-wild type GBM. By using an integrated approach, including proteomics, transcriptomics and metabolic profiling, we identify praja2 as a main component of a signaling network that regulates cancer cell growth and metabolism. We show that praja2 binds and regulates the stability of the Kinase Suppressor of Ras 2 (KSR2) and as consequence, the activity of the downstream AMP-dependent protein kinase (AMPK) in GBM cells. By degrading KSR2, praja2 attenuates the oxidative metabolism and promotes the aerobic glycolysis (Warburg effect). Brain delivery of siRNAs targeting praja2 upregulates KSR2 and negatively impacted on GBM growth, reducing the tumor size and significantly improving the survival rate of treated mice. These data highlight the role of praja2 as an essential regulator of cancer cell metabolism, and as a preferential therapeutic target to suppress GBM growth

2022-06-29 | E-MTAB-11137 | biostudies-arrayexpress

Transcriptional response to TNF-alpha in a panel of 17 human melanoma cell lines

Project description:A panel of 17 human melanoma cell lines with known BRAF and NRAS mutation status was stimulated with TNF-alpha for 72 hours. The goal of the study was to correlate the transcriptional response in BRAF versus NRAS mutated melanoma cell lines.

2014-02-10 | GSE51221 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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