Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Impact of BRAF kinase inhibitors on miRNomes and transcriptomes of melanoma cells (gene expression dataset)

ABSTRACT: Melanoma is an aggressive skin cancer with increasing incidence worldwide. The development of BRAF kinase inhibitors as targeted treatments for patients with BRAF-mutant tumours contributed profoundly to an improved overall survival of patients with metastatic melanoma. Despite these promising results, the emergence of rapid resistance to targeted therapy remains a serious clinical issue. To investigate the impact of BRAF inhibitors on miRNomes and transcriptomes, we used in vitro melanoma models consisting of BRAF inhibitor-sensitive and -resistant cell lines generated in our laboratory. miRNA and gene expression were assessed by microarray analyses of the BRAF inhibitor sensitive melanoma cells A375, IGR37, and 501Mel, as well as on the vemurafenib (PLX4032) - resistant cells A375_XP, IGR37_XP, 501Mel_XP, and dabrafenib (GSK2118436) - resistant cells A375_GP, IGR37_GP, 501Mel_GP. For each cell line the microarray experiment was performed in duplicates.

ORGANISM(S): Homo sapiens

SUBMITTER: Ines Kozar

PROVIDER: E-MTAB-5511 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Impact of BRAF kinase inhibitors on miRNomes and transcriptomes of melanoma cells (miRNA dataset)

Project description:Melanoma is an aggressive skin cancer with increasing incidence worldwide. The development of BRAF kinase inhibitors as targeted treatments for patients with BRAF-mutant tumours contributed profoundly to an improved overall survival of patients with metastatic melanoma. Despite these promising results, the emergence of rapid resistance to targeted therapy remains a serious clinical issue. To investigate the impact of BRAF inhibitors on miRNomes and transcriptomes, we used in vitro melanoma models consisting of BRAF inhibitor-sensitive and -resistant cell lines generated in our laboratory. miRNA and gene expression were assessed by microarray analyses of the BRAF inhibitor sensitive melanoma cells A375, IGR37, and 501Mel, as well as on the vemurafenib (PLX4032) - resistant cells A375_XP, IGR37_XP, 501Mel_XP, and dabrafenib (GSK2118436) - resistant cells A375_GP, IGR37_GP, 501Mel_GP. For each cell line the microarray experiment was performed in duplicates.

2017-03-06 | E-MTAB-5510 | biostudies-arrayexpress

A new ALK isoform transported by extracellular vesicles confers drug resistance to vemurafenib in A375 melanoma cells

Project description:Despite the successful use of drugs targeting the MAPK signaling pathway and immunotherapy in melanoma, the majority of patients with metastatic disease still undergo disease progression indicating a gradual development of therapy resistance. In the present study, microarray analyses were performed on BRAF inhibitor sensitive melanoma cells A375 and corresponding vemurafenib (PLX4032) - resistant cells A375_X1 to describe changes in the transcriptome that might play a role in drug resistance. For each cell line the microarray experiment was performed in duplicates.

2019-02-28 | E-MTAB-6596 | biostudies-arrayexpress

Expression data from BRAF-mutant melanoma cell lines

Project description:Melanoma cell lines were assessed for differences in gene expression patterns between the lines sensitive and resistant to BRAF and MEK inhibitor drugs. 22 BRAF-mutant melanoma cell lines were assessed for response to BRAF and MEK inhibitors in a 3 day drug treatment dose response assay. Based on the IC50, 18 lines were found to be responsive to BRAF or MEK inhibition and 4 were resistant. Normalised gene expression data generated from experimental replicate affymetrix arrays was assessed to identify differential patterns of inherent gene expression between the cell lines grouped as drug-responsive or drug-resistant. This were used to idenify specific candidate genes and pathways associated with inherent BRAF/MEK inhibitor drug resistance in melanoma cells.

2015-08-26 | E-GEOD-45558 | biostudies-arrayexpress

Profiling of the miRNome in melanoma cells under normoxia and hypoxia

Project description:The proteomes and the miRNomes of melanoma cells and secreted vesicles of normoxic and hypoxic A375, 501Mel, MelJuso and IPC298 melanoma cells were characterized. Here are the data related to the miRNome of cell extracts for the 4 cell lines, in normoxia and hypoxia conditions.

2020-03-31 | E-MTAB-8577 | biostudies-arrayexpress

SOX-2 mediated upregulation of CD24 promotes adaptive resistance towards targeted therapy in melanoma

Project description:Melanoma is one of the most aggressive types of skin cancer and is often characterized by a constitutively activate RAS-RAF-MEK-ERK pathway. For targeted therapy, BRAF inhibitors are available that are powerful in the beginning but resistance occurs rather fast. A better understanding of the underlying mechanisms of resistance is urgently needed to increase the success of the treatment. Here, we observed that in targeted therapy resistant, melanoma-derived induced pluripotent cancer cells (iPCCs) SOX2 and CD24 are upregulated. It is known that both SOX2 and CD24 expression promote an undifferentiated and cancer stem cell like phenotype, which is associated with higher therapy resistance. We therefore elucidated the role of SOX2 and CD24 in targeted therapy resistance in more detail. We found that SOX2 and CD24 are upregulated upon BRAF inhibitor treatment and that SOX2 is able to upregulate the expression of CD24 by binding to the CD24 promoter. Furthermore, we show that SOX2 or CD24 overexpression significantly increase the resistance towards BRAF inhibitors, while SOX2 knock-down rendered cell sensitive towards treatment. Moreover, CD24 and SOX2 are able to upregulate Src and STAT3 activity which could contribute to the increased resistance. Importantly, CD24 knockdown or Src inhibition in resistant SOX2 overexpressing cells, the sensitivity towards BRAF inhibitors was re-established. Hence, we suggest a novel mechanism of adaptive resistance whereby BRAF inhibition is circumvented via the upregulation of CD24 by SOX2 resulting in increased activity of Scr and STAT3. Thus, to prevent adaptive resistance it might be beneficial to use Src or STAT3 inhibitors together with MAPK pathway inhibitors.

2018-05-15 | GSE106321 | GEO

Therapy induced tumour secretomes promote resistance and tumour progression

Project description:Drug resistance invariably limits the clinical efficacy of targeted therapy with kinase inhibitors against cancer. We found that targeted therapy with BRAF, ALK, or EGFR inhibitors induces a complex network of secreted signals in drug-stressed melanoma and lung adenocarcinoma cells. This therapy-induced secretome (TIS) stimulates the outgrowth, infiltration and metastasis of drug-resistant cancer clones in the tumour. Additionally, the TIS supports the survival of drug-sensitive cells, contributing to incomplete tumour regression. We used transcriptomic analysis of sensitive tumour cells and xenograft tumours treated with vehicle, vemurafenib, or crizotinib to identify the transcriptional drivers and to dissect the TIS in melanoma (A375, Colo800, UACC62) and lung adenocarcinoma (H3122). In addition, we utilize cell type–specific mRNA purification by translating ribosome affinity purification (TRAP) to identify pathways that are up-regulated in resistant cells (A375R) in response to the regressing tumour microenvironment.

2015-03-26 | GSE64741 | GEO

Low MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma

Project description:Increased MITF expression contributes to melanoma progression and resistance to BRAF pathway inhibition. We show that, unexpectedly, lack of MITF is associated with more severe resistance to a range of inhibitors. Indeed, the presence of endogenous MITF was essential for robust drug responses. Both in primary and acquired resistance, MITF levels inversely correlated with expression of several activated receptor tyrosine kinases, most commonly AXL. The MITF-low/AXL-high/drug resistance phenotype was seen in roughly half of BRAF mutant and the majority of NRAS mutant melanoma cell lines. The dichotomous behavior of MITF in drug response was corroborated in vemurafenib-resistant biopsies, including MITF high and low clones in a relapsed patient. Drug cocktails containing AXL inhibitor enhanced melanoma cell elimination by BRAF or ERK inhibition. Our results demonstrate that a low MITF/AXL ratio predicts early resistance to multiple targeted drugs, and warrant clinical validation of AXL inhibitors to combat resistance of BRAF and NRAS mutant MITF-low melanomas. Experssion analysis by RNAseq of 14 melanoma cell lines.

2014-09-19 | E-GEOD-61544 | biostudies-arrayexpress

SAKE (Single-cell RNA-Seq Analysis and Klustering Evaluation) Identifies Markers of Resistance to Targeted BRAF Inhibitors in Melanoma Cell Populations [10x]

Project description:The goal of this study is to apply the SAKE algorithms to identify drug-resistant cellular populations as human melanoma cells respond to targeted BRAF inhibitors. Single-cell RNA-Seq data from 10x Genomics platform was analyzed to dissect this problem at multiple scales. Data indicates that BRAF inhibitor resistant cells can emerge from rare populations already present before drug application, with SAKE identifying both novel and known markers of resistance

2018-07-01 | GSE108394 | GEO

New compounds triggering endoplasmic reticulum stress exert anti-melanoma effects and overcome BRAF inhibitor resistance

Project description:We discovered and developed a new series of molecules (thiazole benzenesulfonamides). HA15, the lead compound of this series, displayed anti-cancerous activity on all tested melanoma cells including those isolated from patients and those that developed resistance to BRAF inhibitors. Our molecule displayed activity against other liquid and solid tumors. HA15 also exhibited strong efficacy in xenograft mouse models with melanoma cells either sensitive or resistant to BRAF inhibitors. Transcriptomic, proteomic and biochemical studies identified the chaperone BiP/GRP78/HSPA5 as the specific target of HA15 and demonstrated that the interaction increases endoplasmic reticulum (ER) stress, leading to melanoma cell death by concomitant induction of autophagic and apoptotic mechanisms.

2016-06-01 | GSE79071 | GEO

New compounds triggering endoplasmic reticulum stress exert anti-melanoma effects and overcome BRAF inhibitor resistance

2016-06-01 | E-GEOD-79071 | biostudies-arrayexpress

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