Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neuroblastoma RAS viral oncogene homolog (N-RAS) deficiency aggravates liver injury and fibrosis

ABSTRACT: Neuroblastoma RAS viral oncogene homolog (N-RAS) deficiency aggravates liver injury and fibrosis

PROVIDER: PRJNA993123 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Neuroblastoma RAS viral oncogene homolog (N-RAS) deficiency aggravates liver injury and fibrosis

Project description:To gain insight into the differential signaling pathways triggered in N-RAS-/- versus N-RAS+/+ mice during liver injury and fibrosis, we performed microarray analyses of livers 28 days after CCl4 treatment and BDL surgery, respectively. Our findings suggested that increased cell proliferation and matrix deposition as well as loss of cell homeostasis were characteristic of N-RAS-/- after experimental fibrosis. We used microarrays to detail the global programme of gene expression underlying CCl4 and BDL challenge,

2023-07-15 | GSE236915 | GEO

Neuroblastoma RAS viral oncogene homolog (N-RAS) deficiency aggravates liver injury and fibrosis.

Project description:Progressive hepatic damage and fibrosis are major features of chronic liver diseases of different etiology, yet the underlying molecular mechanisms remain to be fully defined. N-RAS, a member of the RAS family of small guanine nucleotide-binding proteins also encompassing the highly homologous H-RAS and K-RAS isoforms, was previously reported to modulate cell death and renal fibrosis; however, its role in liver damage and fibrogenesis remains unknown. Here, we approached this question by using N-RAS deficient (N-RAS-/-) mice and two experimental models of liver injury and fibrosis, namely carbon tetrachloride (CCl4) intoxication and bile duct ligation (BDL). In wild-type (N-RAS+/+) mice both hepatotoxic procedures augmented N-RAS expression in the liver. Compared to N-RAS+/+ counterparts, N-RAS-/- mice subjected to either CCl4 or BDL showed exacerbated liver injury and fibrosis, which was associated with enhanced hepatic stellate cell (HSC) activation and leukocyte infiltration in the damaged liver. At the molecular level, after CCl4 or BDL, N-RAS-/- livers exhibited augmented expression of necroptotic death markers along with JNK1/2 hyperactivation. In line with this, N-RAS ablation in a human hepatocytic cell line resulted in enhanced activation of JNK and necroptosis mediators in response to cell death stimuli. Of note, loss of hepatic N-RAS expression was characteristic of chronic liver disease patients with fibrosis. Collectively, our study unveils a novel role for N-RAS as a negative controller of the progression of liver injury and fibrogenesis, by critically downregulating signaling pathways leading to hepatocyte necroptosis. Furthermore, it suggests that N-RAS may be of potential clinical value as prognostic biomarker of progressive fibrotic liver damage, or as a novel therapeutic target for the treatment of chronic liver disease.

| S-EPMC10415403 | biostudies-literature

Folfirinox + Cetuximab Chemotherapy, in First Line, With Wild RAS and According to BRAF Status in Metastatic Colorectal Cancer

Project description:This retrospective study, will evaluate patient outcomes after triplet chemotherapy (FOLFIRINOX) (5 Fluorouracil + oxaliplatin + irinotecan) plus cetuximab 1st line treatment focusing on efficacy and safety in a RAS (KRAS, NRAS (neuroblastoma rat sarcoma viral oncogene homolog) wild-type metastatic colorectal cancer population, and according to BRAF (murine sarcoma viral oncogene homolog B) status and primary tumor location.

| 2302806 | ecrin-mdr-crc

Generating a RAS expression signature in neuroblastoma

Project description:Mutations affecting the RAS-MAPK pathway frequently occur in relapse neuroblastoma tumors, which suggests that activation of this pathway is associated with a more aggressive phenotype. To explore this hypothesis we generated several model systems to define a neuroblastoma RAS-MAPK pathway signature. We could show that activation of this pathway in primary tumors indeed correlates with poor survival and is associated with known activating mutations in ALK and other RAS-MAPK pathway genes. From integrative analysis we could show that mutations in PHOX2B, CIC and DMD are also associated with an activated RAS-MAPK pathway. Mutation of PHOX2B and deletion of CIC in neuroblastoma cell lines induces activation of the RAS-MAPK pathway. This activation was independent of phosphorylated ERK in the CIC knock out systems. Furthermore, deletion of CIC causes a significant increase in tumor growth in vivo. These results show that the RAS-MAPK pathway is involved in tumor progression, and establish CIC as a powerful tumor suppressor that functions downstream of this pathway in neuroblastoma.

2018-08-22 | GSE115406 | GEO

Generating a RAS expression signature in neuroblastoma

Project description:Generating a RAS expression signature in neuroblastoma

| PRJNA474895 | ENA

A Drosophila proto-oncogene homolog controls aggression via aminergic neurons

Project description:A Drosophila proto-oncogene homolog controls aggression via aminergic neurons

| PRJNA625242 | ENA

Gene expression changes induced by K-ras oncogene in the human pancreatic duct epithelial cell line (H6c7)

Project description:k-ras oncogene was transduced into the HPV16-E6E7 immortalized normal human pancreatic duct epithelial cell line (H6c7) to generate a stable K-ras oncogene-expressing cell line (H6c7-Kr). The gene expression profile of the H6c7-Kr cells was compared to that of H6c7 cells. We have excluded (subtracted) genes that were deregulated by transduction of the construct used for K-ras oncogene expression. Keywords: parallel sample

2005-01-11 | GSE1955 | GEO

Transcription profiling of human pancreatic duct epithelial cell line (H6c7) Gene expression changes induced by K-ras oncogene in the

2008-06-11 | E-GEOD-1955 | biostudies-arrayexpress

Neuroblastoma RAS viral oncogene homolog mRNA is differentially spliced to give five distinct isoforms: implications for melanoma therapy.

Project description:Neuroblastoma RAS viral oncogene homolog is a commonly mutated oncogene in melanoma, and therapeutic targeting of neuroblastoma RAS viral oncogene homolog has proven difficult. We characterized the expression and phenotypic functions of five recently discovered splice isoforms of neuroblastoma RAS viral oncogene homolog in melanoma. Canonical neuroblastoma RAS viral oncogene homolog (isoform-1) was expressed to the highest degree and its expression was significantly increased in melanoma metastases compared to primary lesions. Isoform-5 expression in metastases showed a significant, positive correlation with survival and tumours over-expressing isoform-5 had significantly decreased growth in a xenograft model. In contrast, over-expression of any isoform resulted in enhanced proliferation, and invasiveness was increased with over-expression of isoform-1 or isoform-2. Downstream signalling analysis indicated that the isoforms signalled differentially through the mitogen-activated protein kinase and PI3K pathways and A375 cells over-expressing isoform-2 or isoform-5 showed resistance to vemurafenib treatment in vitro. The neuroblastoma RAS viral oncogene homolog isoforms appear to play varying roles in melanoma phenotype and could potentially serve as biomarkers for therapeutic response and disease prognosis.

| S-EPMC7088457 | biostudies-literature

A Study of ELI-002 in Subjects With KRAS Mutated Pancreatic Ductal Adenocarcinoma (PDAC) and Other Solid Tumors

Project description:This is a Phase 1 study to assess the safety and efficacy of ELI-002 immunotherapy (a lipid-conjugated immune-stimulatory oligonucleotide [Amph-CpG-7909] plus a mixture of lipid-conjugated peptide-based antigens [Amph-Peptides]) as adjuvant treatment of minimal residual disease (MRD) in subjects with KRAS/neuroblastoma ras viral oncogene homolog (NRAS) mutated PDAC or other solid tumors.

| 2374931 | ecrin-mdr-crc

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