Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Elucidation of Ras homologous A: Systematic approach to identify potential signaling in gastric cancer

ABSTRACT: Elucidation of Ras homologous A: Systematic approach to identify potential signaling in gastric cancer

PROVIDER: PRJNA557256 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Elucidation of Ras homologous A: Systematic approach to identify potential signaling in gastric cancer

Project description:Previously, we identified Ras homologous A (RHOA) as a major signalling hub in gastric cancer (GC), the third-most common cause of cancer death in the world, prompting us to rationally design an efficacious inhibitor of this oncogenic GTPase. Here, based on that previous work, we extend those computational analyses, and in silico modeling approaches, to further pharmacologically optimize anti-RHOA hydrazide derivatives for greater anti-GC potency. Two of these, JK-136 and JK-139, potently inhibited cell viability and migration/invasion of GC cell lines, and mouse xenografts, diversely expressing RHOA. Moreover, JK-136’s binding affinity for RHOA was >140-fold greater than Rhosin, a nonclinical RHOA inhibitor. Network analysis of JK-136/139-associated transcriptomes showed different functional contexts, compared to those following treatment with Rhosin. We strongly assert that identifying and targeting oncogenic signalling hubs, such as RHOA, represents an emerging strategy for the design, characterization, and translation of new antineoplastics, against gastric and other cancers.

2020-05-25 | GSE135068 | GEO

Systematic elucidation of genetic mechanisms underlying cholesterol uptake

Project description:Systematic elucidation of genetic mechanisms underlying cholesterol uptake

2023-04-21 | GSE229650 | GEO

Systematic elucidation of neuron-astrocyte interaction in models of amyotrophic lateral sclerosis using multi-modal integrated bioinformatics workflow

Project description:Cell-to-cell communications are critical determinants of pathophysiological phenotypes, but methodologies for their systematic elucidation are lacking. Herein, we propose an approach for the Systematic Elucidation and Assessment of Regulatory Cell-to-cell Interaction Networks (SEARCHIN) to elucidate ligand-mediated interactions between distinct cellular compartments. To test this approach, we selected a model of amyotrophic lateral sclerosis (ALS), in which astrocytes expressing mutant superoxide dismutase-1 (mutSOD1) kill wild-type motor neurons (MNs) by an unknown mechanism. Integrative analysis that combines proteomics and regulatory network analysis infers the interaction between astrocyte-released amyloid precursor protein (APP) and death receptor-6 (DR6) on MNs as the top predicted ligand-receptor pair. The inferred deleterious role of APP and DR6 is confirmed in vitro in models of ALS. Moreover, the DR6 knockdown in MNs of transgenic mutSOD1 mice attenuates the ALS-like phenotype. Our results support the usefulness of integrative, systems biology approach to gain insights into complex neurobiological disease processes as in ALS and posit that the proposed methodology is not restricted to this biological context and could be used in a variety of other non-cell-autonomous communication mechanisms.

2021-09-09 | PXD021773 | Pride

Systematic Elucidation of the Mechanism of Quercetin against Gastric Cancer via Network Pharmacology Approach.

Project description: Not available

| S-EPMC7486643 | biostudies-literature

Elucidation of FOXP1 target genes in DLBCL by RNA-Seq

Project description:Elucidation of FOXP1 target genes by RNA-Seq of DLBCL cell lines transfected with siRNAs targeting FOXP1 expression

2015-11-30 | E-MTAB-3740 | biostudies-arrayexpress

Serum-dependent transcriptional networks identify distinct functional roles for H-ras and N-ras

Project description:Serum-dependent transcriptional networks identify distinct functional roles for H-ras and N-ras during initial stages of the cell cycle Using oligonucleotide microarrays, we compared gene expression transcriptional profiles corresponding to the initial cell cycle stages of mouse fibroblasts lacking H-Ras and/or NRas with those of matching, WT controls. The similarity of transcription profiles among serum-starved fibroblasts of all different WT and ras knockout genotypes tested, indicated that H-Ras and N-Ras do not play significant roles in control of transcriptional responses to serum deprivation stress. In contrast, genomic disruption of H-ras or N-ras, individually or in combination, determined highly specific, differential gene expression profiles in response to post-starvation stimulation with serum for 1 hour (G0/G1 transition) or for 8 hours (mid-G1 progression). The absence of N-Ras caused significantly higher changes than the absence of H-Ras on the wave of transcriptional activation linked to G0/G1 transition. In contrast, the absence of H-Ras affected more potently the profile of the transcriptional wave detected during mid-G1 progression. Functional analysis demonstrated a predominant functional association of H-Ras with growth and proliferation, whereas N-Ras exhibited a closer functional link to development or cell cycle regulation as well as immunomodulation and apoptosis. Mechanistic analysis indicated that ERK-dependent activation of Stat1 mediates the regulatory effect of N-Ras on defense and immunity, whereas the pro-apoptotic effects of N-Ras are mediated through ERK and p38 signaling. Our observations support previous reports of an absolute requirement for different peaks of Ras activity during the initial stages of the cell cycle and confirm the notion of functional specificity for the H-Ras and N-Ras isoforms. Keywords: different gene KO mice and time course

2009-09-01 | GSE14829 | GEO

Ephexin1 cooperates with K-Ras to promote oncogenic Ras-driven tumorigenesis

Project description:Ephexin1 was initially identified as a neuronal guanine nucleotide exchange factor involved in the control of neuronal development and synaptic homeostasis. Here, we demonstrate that the induction of Ephexin1 expression by an oncogenic K-Ras mutation amplifies the MAPK signaling via direct interaction with oncogenic Ras and contributes to colon and lung tumorigenesis. Ephexin1 cooperates with mutant Ras to accelerate skin tumorigenesis in vivo. In addition, we have demonstrated that the functionally relevant interaction between oncogenic K-Ras and Ephexin1. Together, these findings suggest that Ephexin1 serves as a positive regulator of Ras-driven oncogenesis and potentially represents a novel target for therapeutic intervention.

2021-10-27 | GSE147809 | GEO

GNPS - Persicamidine structure elucidation

Project description:Mass spectrometry data for structure elucidation of Persicamidines

2022-11-16 | MSV000090724 | GNPS

Differential gene expression in Ki-RAS and Ha-RAS cell lines.

Project description:Comparison of gene expression in Ha-RAS transformed cells versus untransformed Caco-2. Comparison of gene expression in Ki-RAS transformed cells versus untransformed Caco-2.

2009-04-07 | GSE12203 | GEO

Ephexin1 cooperates with K-Ras to promote oncogenic Ras-driven tumorigenesis

Project description:Ephexin1 cooperates with K-Ras to promote oncogenic Ras-driven tumorigenesis

| PRJNA619876 | ENA