Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A kinase inhibitor screen identifies a dual cdc7/CDK9 inhibitor to sensitise triple-negative breast cancer to EGFR-targeted therapy

ABSTRACT: Purpose: To investigate the impact of combined cdc7, CDK9 and EGFR inhibition on the transcriptomic profile of EGFR-TKI-resistant TNBC cells using high-throughput RNA sequencing. Methods: EGFR-TKI-resistant TNBC cell lines (Hs578T and SKBR7) were treated with DMSO, lapatinib (3.16 µM), PHA-767491 (1 µM) or co-treated with lapatinib (3.16 µM) & PHA-767491 (1 µM) for 6 hours. RNA was isolated with RNeasy Plus Mini Kit as described by manufacturer (QIAGEN, Cat. 74136). Transcriptome RNA-Sequencing (RNA-Seq) was performed using Illumina high-throughput RNA sequencing. Results:we mapped about 40 million sequence reads per sample to the human genome (build hg38). RNA-Seq data was normalised by TMM using EdgeR’s normalisation-factor followed by quantile normalisation and presented in Log2 fold change (Log2 FC) scales.Genes with significant down- or up-regulation (Log2 FC ≥ |0.5|) under indicated conditions were analysed by web-based functional analysis tool Ingenuity pathway Analysis (IPA) to visualise and annotate their biological functions and pathways. Conclusions: 1387 and 2747 genes were down-regulated in co-treated Hs578T and SKBR7 cells, respectively. 2614 genes were up-regulated by co-treatment in Hs578T cells, whilst 243 genes were up-regulated by the same treatment in SKBR7 cells. We identified 845 commonly differentially expressed transcripts in both HS578T and SKBR7 cells after co-treatment of which 141 transcripts were up-regulated and 704 transcripts were down-regulated. 34 of these commonly differentially expressed transcripts were linked to metastasis-free survival in TNBC patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE131375 | GEO | 2019/07/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Integrative analysis of genomic amplification-dependent expression and loss-of-function screen identifies ASAP1 as a driver gene in triple negative breast cancer progression

Project description:Purpose: To investigate the impact of ASAP1 depletion on the transcriptomic profile of TNBC cells using TempO-Seq-based high-throughput RNA sequencing. Methods: Three TNBC cell lines (BT549, SUM149PT and Hs578T) were treated with siRNA control or siRNA targeting ASAP1 for 72 hours. RNA was isolated with RNeasy Plus Mini Kit as described by manufacturer (QIAGEN, Cat. 74136). Transcriptome RNA-Sequencing (TempO-Seq) was performed using Illumina high-throughput RNA sequencing. Results: We mapped about 7 million sequence reads per sample to the human genome. Normalization and differential expression analysis were performed using DESeq2 package. Genes with significant down- or up-regulation (Log2 FC ≥ |1|) under indicated conditions were analysed by web-based functional analysis tool Metascape to visualise and annotate their biological functions and pathways. Conclusions: Genes with 2-fold changes (absolute Log2 FC ≥ 1) in down- or up-regulation were selected in BT549 (311 down / 495 up), Hs578T (133 down / 117 up) and SUM149PT (500 down / 401 up) cells, respectively. Consequently, 95 DEGs were downregulated, and 79 DEGs upregulated in ≥ 2/3 of the TNBC cell lines, in total 174 DEGs, which were considered as common DEGs that were susceptible to the depletion of the amplification-dependent ASAP1. 53 of these commonly differentially expressed transcripts were linked to relapse-free survival in TNBC patients.

2020-05-19 | GSE134803 | GEO

Effect on gene expression of CDK12/13 inhibition by THZ531 in combination with lapatinib or nilotinib in Hs578T TNBC cells

Project description:We performed whole transcriptome expression profiling in Hs578T cells after treatment with THZ531, nilotinib, lapatinib or a combination thereof to study the effect of these combination treatments on the transcriptome.

2023-04-01 | GSE210987 | GEO

RNA-seq analysis revealed that lapatinib-induced keratinocyte apoptosis is related to mitochondrial dysfunction and DNA damage

Project description:Lapatinib, a widely used dual EGFR and ERBB2 inhibitor, have been seriously limited due to skin rash, one of its most common adverse effects caused by EGFR inhibitors in clinical. Here, we found that lapatinib could induce mitochondrial dysfunction, lead to DNA damage and finally cause apoptosis of keratinocytes according to the RNA-sequencing clues. Mechanistically, downregulated expression of DNA repair protein HMGB1 played a critical role in these toxic reaction processes. We found that saikosaponin A could significantly rescue the reduced HMGB1 transcription, which could alleviate lapatinib-induced DNA damage, inhibit keratinocyte apoptosis and further prevent the cutaneous toxicity in mice caused by lapatinib.

2022-12-01 | GSE195713 | GEO

Expression data from MM231 and MM231-FGD5-cas9 breast cancer cells

Project description:To identify the differiational genes and pathways in MM231 and MM231-FGD5-cas9, we examined the microarray gene expression profile of MM231 breast cancer cells vs FGD5-cas9 cells. Ectopic expression or activation of EGFR is found in most TNBCs, and EGFR inhibitors can suppress TNBC growth in vitro. However, these agents exhibit limited efficacy in TNBC patients, possibly due to the nonkinase oncogenic functions of EGFR and the compensatory effects of other oncogenic activities following anti-EGFR therapy. Here, we identified a positive correlation between EGFR and FGD5 expression in TNBC samples. FGD5 deletion attenuated TNBC initiation and progression by decreasing EGFR stability and expression. Moreover, the proteins involved in mutual compensation of EGFR signaling were significantly downregulated in FGD5-deleted TNBC cells. Mechanistically, FGD5 interacted with EGFR to maintain EGFR stability by impeding EGFR ubiquitylation and degradation mediated by the E3 ligase ITCH; disrupting the FGD5-EGFR interaction accelerated EGFR degradation and produced robust anti-TNBC activity. Our study shows that targeted degradation of EGFR through disrupting the FGD5-EGFR interaction is a promising therapeutic strategy for the TNBC subtype of breast cancer.

2020-01-27 | GSE144260 | GEO

Effect on gene expression of CDK12/13 inhibition by THZ531 in combination with lapatinib or nilotinib in Hs578T TNBC cells

Project description:Effect on gene expression of CDK12/13 inhibition by THZ531 in combination with lapatinib or nilotinib in Hs578T TNBC cells

| PRJNA868417 | ENA

Gene expression profile in breast cancer cell lines using RNA sequencing

Project description:In order to identify novel molecular targets associated with TNBC progression, we initially performed transcriptome analysis using RNA sequencing in breast cancer cell lines, classified as either the luminal subtype (MCF-7, T47D, ZR-75B) or basal-like subtype (MDA-MB-231, MDA-MB-435, Hs578T).

2017-08-09 | GSE100878 | GEO

Next-Generation Sequencing for Whole Transcriptome Analysis in Scrambled Control and EGFR Knockdown Cells Cultured under Normoxia and Hypoxia

Project description:Purpose: The goal of this study is to identify the mRNA clusters that are regulated by EGFR under normoxia or hypoxia. Method: Total RNAs were extracted from HeLa cells expressing scrambled control or EGFR shRNA-E1 that cultured under normoxia or hypoxia (1% O2) for 24h. Customized Next-Generation RNA Deep Sequencing, including both small RNA application and whole transcriptome analysis, was performed according to the standard procedure instructed by Applied Biosystems. For whole transcriptome analysis, SOLiD fragment colorspace transcriptome reads (50nt) were mapped to the human genome (hg19) and assigned to ensemble transcripts using Bioscope 1.3.1 (Life Technologies). The values of reads per kilobase per million reads (RPKM) were determined by Bioscope 1.3.1 CountTags tool using default parameters. Primary alignments with a minimum mapping quality of 10 and minimum alignment score of 10 were counted. Results: Deep sequencing analysis identified subclasses of mRNAs that were affected by EGFR either under normoxia or hypoxia. EGFR-regulated mRNAs (with Log2 fold-change affected by EGFR ≥ 0.4 or ≤ -0.4) were sorted and over-lapped with mRNAs that were targeted (based on published data and TargetScan prediction with total context score ≤ -0.20) by the top miRNA candidates affected by EGFR under hypoxia, resulting in 439 mRNAs that regulated by EGFR and likely targeted by the miRNA candidates in response to hypoxia. Conclusion: Whole transcriptome analysis revealed a novel cluster of mRNAs that are likely regulated by EGFR through miRNAs in response to hypoxic stress.

2013-10-01 | GSE44801 | GEO

activated sludge metagenome

Project description:PHA-producing WAS 16S rRNA transcripts

| PRJNA218058 | ENA

Inhibition of ABCB1 Overcomes Cancer Stem Cell-like Properties and Acquired Resistance to MET inhibitor in Non-Small Cell Lung Cancer

Project description:Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations have shown a dramatic response to EGFR inhibitors (EGFR-TKI). EGFR T790M mutation and MET amplification have been recognized as major mechanisms of acquired resistance to EGFR-TKI. Therefore, MET inhibitors have recently been used in NSCLC patients in clinical trials. In this study, we tried to identify the mechanism of acquired resistance to MET inhibitor. We analyzed the antitumor effects of two MET inhibitors, PHA-665752 and crizotinib, in 10 NSCLC cell lines. EBC1 cells with MET amplification were the only cells that were sensitive to both MET inhibitors. We established PHA-665752-resistant EBC1 cells, namely EBC1-R cells. EBC1-R cells showed overexpression of ATP-binding cassette sub-family B member 1 (ABCB1) as well as phosphorylation of MET. EBC1-R cells grew as cell spheres that exhibited cancer stem cell-like (CSC) properties and epithelial mesenchymal transition (EMT). The levels of two miRNAs, miR-374a and miR-138 which targeted ABCB1, were decreased in EBC1-R cells. ABCB1 siRNA and ABCB1 inhibitor elacridar could reduce sphere numbers and suppress EMT. Elacridar could also reverse the resistance to PHA-665752 in EBC1-R cells. Our study demonstrated that ABCB1 overexpression which was associated with CSC properties and EMT was involved in the acquired resistance to MET inhibitor. Inhibition of ABCB1 might be a novel therapeutic strategy for NSCLC patients with acquired resistance to MET inhibitor.

2015-03-07 | GSE66604 | GEO

Protein Tyrosine Phosphatase UBASH3B is Overexpressed in Triple-Negative Breast Cancer and Promotes Invasion and Metastasis

Project description:Efforts to improve the clinical outcome of highly aggressive triplenegative breast cancer (TNBC) have been hindered by the lack of effective targeted therapies. Hence, it is important to identify the specific gene targets/pathways driving the invasive phenotype to develop more effective therapeutics. Here we show that UBASH3B (ubiquitin associated and SH3 domain containing B), a protein tyrosine phosphatase, is overexpressed in TNBC, where it supports malignant growth, invasion and metastasis in large through modulating EGFR. We also show that UBASH3B is a functional target of anti-invasive miR-200a that is downregulated in TNBC. Importantly, the oncogenic potential of UBASH3B is dependent on its tyrosine phosphatase activity, which targets CBL ubiquitin ligase for dephosphorylation and inactivation, leading to EGFR upregulation. Thus, UBASH3B may function as a crucial node in bridging multiple invasion-promoting pathways, thus providing a potential new therapeutic target for TNBC. Breast cancer tissues and breast cancer cell lines

2013-06-01 | E-GEOD-36693 | biostudies-arrayexpress

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