Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

54 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-seq of FGFR2 fusion+ ICC cell lines (ICC21 and ICC10-6) treated with Infigratinib or/and Afatinib against untreated control

ABSTRACT: Genomic alterations that activate Fibroblast Growth Factor Receptor 2 (FGFR2) are common in intrahepatic cholangiocarcinoma (ICC), a deadly bile duct malignancy. FGFR kinase inhibitors (FGFRi) have shown promising efficacy against FGFR2+ ICC in clinical trials, leading to the regulatory approval of the ATP-competitive FGFR inhibitors, pemigatinib and infigratinib (BGJ398), for this subset of patients who failed standard treatment . However, the objective response rate (ORR) for each FGFR inhibitor (FGFRi) studied to date in FGFR2+ ICC is <45% and disease progression invariably arises within ~6-12 months. By employing high-throughput drug screens and signaling studies, we identified signaling feedback via the EGFR pathway as a major mediator of adaptive resistance to FGFR kinase inhibition in a set of patient-derived ICC models. To further gain insights into the synergistic effects of the EGFR/FGFR combination and address the mechanisms underlying the survival pathway reactivation, we performed RNA sequencing in our FGFR-driven ICC models (ICC21 and ICC10-6). For these studies, we treated FGFR2 fusion+ ICC cell lines ICC21/ICC10-6 with four conditions (DMSO/Infigratinib/Afatinib/Combo) for 4 hours followed by RNA sequencing.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Homo sapiens

SUBMITTER: Yuanli Zhen

PROVIDER: E-MTAB-11324 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

FGFR inhibition blocks NF-ĸB-dependent glucose metabolism and confers metabolic vulnerabilities in cholangiocarcinoma

Project description:Genomic alterations that activate FGFR2 are common in intrahepatic cholangiocarcinoma (ICC) and confer sensitivity to treatment with FGFR inhibitors. However, the depth and duration of responses are often limited. Elucidating the FGFR2-driven oncogenic program and the adaptions to FGFR inhibition is needed to gain insight into the biology of these tumors and inform future therapeutic development. Here, we conducted transcriptomic analysis of patient-derived models to define the pathways that fuel tumor growth downstream of oncogenic FGFR2 signaling in ICC and to uncover compensatory mechanisms associated with pathway inhibition. For these studies, we performed RNA sequencing in our FGFR-driven ICC models, including cell line ICC13-7 , PDX MG69 and MG212. We treated ICC13-7 with DMSO or 75 nM Futibatinib for 4/12/24 hours, MG69 with vehicle or Futibatinib for 14 days and MG212 with vehicle or Pemigatinib for 11 days followed by RNA sequencing. In addition, ICC13-7 cells were transfected with siScramble and siRELA and followed by RNA sequencing.

2024-03-20 | GSE241735 | GEO

RNaseq of two human LUAD cell lines with knockout of STK11, KEAP1, both genes or no genes.

Project description:We investigated how selective mutation in STK11 or KEAP1 alters the transcriptional profile of cancer cells, and how the transcriptional profile of co-mutant cells might uniquely affect cancer-related pathways including control of proliferative potential, metabolic homeostasis, and cell death. We performed bulk RNAseq on none, single or double mutation of these genes in single cell knockout clones (n=3 per group) from both H358 and H292 cell lines.

2020-11-12 | E-MTAB-9724 | biostudies-arrayexpress

RNA-Seq of synovial tissue biopsies from individuals with rheumatoid arthritis from the R4RA randomised clinical trial

Project description:Transcriptomic profiles of synovial biopsies of rheumatoid arthritis (RA) patients who were recruited into the R4RA randomised clinical trial. Patients were randomised to treatment with rituximab or tocilizumab. All patients fulfilled the 2010 ACR/EULAR classification criteria for RA and were eligible for treatment with rituximab therapy according to UK NICE guidelines, i.e. failing or intolerant to csDMARD therapy and at least one biologic therapy (excluding trial IMPs) were recruited when fulfilling the trial inclusion/exclusion criteria. For the full study protocol and baseline patient characteristics see Humby et al (2021) The Lancet 397(10271): 305-17. PMID: 33485455.

2022-04-26 | E-MTAB-11611 | biostudies-arrayexpress

Effect of Microcystin-LR and cylindrospermopsin (CYN) on gene expression in human hepatocytes, HepaRG cells and HCC HepG2 cells.

Project description:Human hepatocytes, HepaRG cells and HCC HepG2 cells were treated with 50nM of Microcystin-LR and cylindrospermopsin (CYN) to observe changes in gene expression.

2023-05-12 | E-MTAB-12881 | biostudies-arrayexpress

Effect of miR-99b-5p on global gene expression in PC3 cells

Project description:We analyzed the effect of negative control mimic and miR-99b-5p mimic on global gene expression in PC3 cells

2021-12-30 | E-MTAB-10350 | biostudies-arrayexpress

Effect of miR-214-3p knockdown on global gene expression in prostate cancer cells

Project description:We analyzed the effect of knockdown of miR-214 compared to wild type on the expression of genes and pathways involved in prostate cancer cells.

2021-12-31 | E-MTAB-10782 | biostudies-arrayexpress

Effect of Cadmiun and Perfluorooctanoic acid (PFOAs) chemicals on global gene expression in liver cells

Project description:We chronically exposed HepaRG (differentiated hepatic cells that retain primary human hepatocytes characteristics) and HepaG2 (liver hepatocarcinoma cells) liver cells to physiologically relevant concentrations of Cadmiun and PFOAs chemicals (10nM) to observed how these affect global gene expression in these cellular models.

2022-05-15 | E-MTAB-11670 | biostudies-arrayexpress

RNA seq of mouse bone marrow derived macrophages treated with Debaryomyces hansenii against untreated controls

Project description:We found that the fungus, Debaryomyces hansenii (D. hansenii), is enriched in inflamed intestinal tissue from patients of Crohn's disease and its administration to mice impairs colonic wound healing in multiple models of colonic injury and repair. To understand the mechanism, we isolated bone marrow derived macrophages from mice and stimulated them in vitro with a pure isolate of D. hansenii. Total RNA was isolated at multiple time points and assayed for transcriptomic analysis.

2021-04-14 | E-MTAB-9806 | biostudies-arrayexpress

Phosphoproteomics of truncated FGFR2, a clinically actionable oncogene in multiple cancers

Project description:Somatic hotspot mutations and structural amplifications and fusions affecting fibroblast growth factor receptor 2 (FGFR2) occur in multiple cancer types. However, clinical responses to FGFR inhibitors (FGFRi) have remained variable, emphasizing a need to better understand which FGFR2 alterations are oncogenic and targetable. Here we applied transposon-based screening and tumor modelling in mice to uncover truncation of exon (E) 18 of Fgfr2 as a potent driver mutation. Human oncogenomic datasets revealed a diverse set of FGFR2 alterations, including rearrangements (REs), E1-E17 partial amplifications, and E18 nonsense and frameshift mutations, each causing transcription of E18-truncated FGFR2 (FGFR2deltaE18). Somatic modelling in mice and human tumor cell lines using a compendium of FGFR2deltaE18 and full-length variants identified FGFR2deltaE18-truncation as potent single-driver alteration in cancer. Here we show the phosphoproteomic landscape of FGFR2 variants in murine epithelial cell (MEC) lines and mouse tumors. Global (STY) phosphoproteomics using IMAC and phosphotyrosine phosphoproteomics using pTyr IP’s are combined with DIA protein expression data to uncover oncogenic signaling of clinically-relevant FGFR2 variants.

2022-06-06 | PXD031711 | Pride

The developing lens transcriptome depends upon a counterbalance of Fgfr2- and Pten-regulated downstream signaling and transcription factor targets

Project description:FGFR signaling plays important roles in development and disease pathogenesis. FGFR activation initiates phosphorylation-driven signaling cascades, most notably the RAS-RAF-MEK-ERK cascade and the PI3K-AKT cascade. PTEN antagonizes FGFR signaling by reducing both AKT and ERK activation. Lenses lacking FGFR2 exhibit lower levels of ERK and AKT phosphorylation accompanied by abnormally small lenses, widespread apoptosis, and defective fiber cell differentiation. In contrast, simultaneous deletion of both Fgfr2 and Pten restores ERK and AKT activation levels as well as lens size, cell survival and several aspects of fiber cell differentiation. A transcriptomic analysis of mouse lenses lacking Fgfr2, Pten or both Fgfr2 and Pten revealed molecular mechanisms that might explain how FGFR2 and PTEN signaling interact during development. The FGFR2-deficient lens transcriptome suggested an overall loss of fiber cell identity with deregulated expression of 1,448 genes, nearly 60% of which returned to normal expression levels in lenses lacking both Fgfr2 and Pten. A specific set of parameters based on expression levels in each genotype identified 68 high priority candidate genes. The homeobox transcription factor, NKX6-1, encoded by one of these genes, had at least one binding motif in the putative promoters of 53 of these 68 genes. Furthermore, NKX6-1 activated the expression of the high priority candidate Rasgrp1, a RAS-activating guanine nucleotide exchange factor. Together, these data suggest a novel regulatory module in which NKX6-1 activates the expression of Rasgrp1 to restore the balance of ERK and AKT activation in the absence of both FGFR2 and PTEN.

2020-02-28 | GSE132945 | GEO

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