Min Huang Similar Datasets
Project description:Introduction: Overcoming of acquired resistance to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) is an intractable obstacle for many clinical oncologists. The mechanisms of resistance to EGFR-TKIs are very complex. Long non-coding RNAs (lncRNAs) may play an important role in cancer development and metastasis. However, the biological process between lncRNAs and drug resistance to EGFR mutated lung cancer largely unknown. Methods: Osimertinib and afatinib-resistant EGFR-mutated lung cancer cells were established using by a stepwise method. Microarray analysis of non-coding and coding RNAs was performed using parental and resistant EGFR-mutant NSCLC cells. Results: Microarray analysis was evaluated by bioinformatics analysis through medical-industrial collaboration. CRNDE and DGCR5 lncRNAs were highly expressed in EGFR-TKIs-resistant cells. CRNDE binds to eIF4A3 protein, down-regulates eIF4A3 and MUC1 expression, and down-regulates p-EGFR expression. CRNDE inhibition activated the eIF4A3/MUC1/EGFR signaling pathway and apoptotic activity and restored sensitivity to EGFR-TKIs. Conclusions: We identified lncRNA CRNDE associated with resistance to EGFR-TKIs in EGFR-mutant NSCLC cells. CRNDE may be a novel therapeutic target for EGFR mutant NSCLC patients.
2021-04-28 | GSE163913 | GEO
Project description:Purpose: The aim of this study is to compare the differentially expressed transcriptome of TKI resistance NSCLC cells and their parental cells Methods: mRNA profiles of the TKI-resistant NSCLC cells and their parental cells were generated by deep sequencing using Illumina HiSeq4000. Clean RNA-seq data was quantified and analyzed using the CLC genomics workbench software version 11.0 (Qiagen, Hilden, Germany). Results: In the current study, we established three EGFR-TKI-resistant cell lines and analyzed their expression profiles by RNA sequencing. We mapped about 30 million sequence reads per sample to the human genome (hg38) sequence and identified 21,463 transcripts in the parental and TKI-resistant NSCLC cells. Over 10% of the transcripts showed differential expression between the parental andTKI-resistant NSCLC cells, with a fold change ≥1.5 and p value <0.05. Transcriptome data analysis revealed the existence of significant overlaps and significant upregulation of epithelial-mesenchymal transition (EMT) pathway in the three cell lines with EGFR-TKI resistance. Conclusions: Our results showed that RNA-seq based transcriptome characterization offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within TKI-resistant NSCLC cells.
2023-07-31 | GSE156054 | GEO
Project description:We have established a Genfitnib resistant cell line, Ire, from a NSCLC cell line, PE089, with deletion of exon 19 in EGFR. RNA-sequencing analysis was performed to analyze the diffreential gene expression between thes two cell lines
2025-03-22 | GSE262345 | GEO
Project description:Non-small cell lung cancers (NSCLCs) harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as erlotinib and geffitinib. However, nearly all patients show relapse within 1 year after initial treatment. We used microarrays to detail global gene expression changes in EGFR mutant cells vs. WT cells responding to erlotinib. 4 EGFR mutant and 4 WT NSCLC cells were treated with or without erlotinib for 24 hr, followed by RNA extraction and hybridization on Affymetrix microarrays.
2014-05-16 | E-GEOD-57156 | biostudies-arrayexpress
Project description:Epidermal growth factor receptor (EGFR) inhibitors, as targeted therapies for non-small-cell lung cancer (NSCLC), have significantly enhanced patient survival and quality of life. However, despite these advancements, a significant proportion of patients exhibit resistance to EGFR inhibitors, limiting their overall treatment effectiveness. This study investigates the synergistic effects of combining Paeoniae Radix (PR) with the EGFR inhibitors erlotinib and gefitinib to overcome this resistance. The transcriptomic analysis of PR treatment revealed its potential to reverse the gene signature associated with resistance to EGFR inhibitors, as identified through analysis of a cell line database in EGFR mutant NSCLC. Combination treatment experiments validated that PR increased responsiveness to erlotinib and gefitinib in H1650 and H1975 NSCLC cells. By combining molecular experiments and transcriptome analysis, we found that PR may suppress resistance by modulating the Aurora B and apoptosis pathways. Notably, the combination therapy upregulated the apoptosis pathway and downregulated the Aurora B pathway more than single drug treatments. These results may contribute to the development of natural product-based combination therapeutic strategies to inhibit drug resistance in NSCLC.
2024-03-24 | GSE261880 | GEO
Project description:Exosomal miRNAs involved in resistance to osimertinib in EGFR-mutant NSCLC cells were successfully identified through the microoarray analysis.
2021-06-15 | GSE165540 | GEO
Project description:Bidkhori2012 - normal EGFR signalling
The paper describes and compares two models on EGFR signalling between normal and NSCLC cells. Moreover, it is shown that ERK (MAPK), STAT and Akt factor's activation pattern are different between normal and NSCLA models. This model corresponds to EGFR signalling in normal cells.
Created by The MathWorks, Inc. SimBiology tool, Version 3.3
This model is described in the article:
Modeling of tumor progression in NSCLC and intrinsic resistance to TKI in loss of PTEN expression.
Bidkhori G, Moeini A, Masoudi-Nejad A
PloS one [2012, 7(10):e48004]
Abstract:
EGFR signaling plays a very important role in NSCLC. It activates Ras/ERK, PI3K/Akt and STAT activation pathways. These are the main pathways for cell proliferation and survival. We have developed two mathematical models to relate to the different EGFR signaling in NSCLC and normal cells in the presence or absence of EGFR and PTEN mutations. The dynamics of downstream signaling pathways vary in the disease state and activation of some factors can be indicative of drug resistance. Our simulation denotes the effect of EGFR mutations and increased expression of certain factors in NSCLC EGFR signaling on each of the three pathways where levels of pERK, pSTAT and pAkt are increased. Over activation of ERK, Akt and STAT3 which are the main cell proliferation and survival factors act as promoting factors for tumor progression in NSCLC. In case of loss of PTEN, Akt activity level is considerably increased. Our simulation results show that in the presence of erlotinib, downstream factors i.e. pAkt, pSTAT3 and pERK are inhibited. However, in case of loss of PTEN expression in the presence of erlotinib, pAkt level would not decrease which demonstrates that these cells are resistant to erlotinib.
This model is hosted on BioModels Database
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by: MODEL1304020000
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000452 | BioModels
Project description:The goal of this study was to compare the transcriptome (RNA-seq) of EGFR TKI sensitive NSCLC cells with that of cells with acquired resistance to erlotinib. HCC827 and HCC4006 cells were continuously cultured in erlotinib until erlotinib resistant (ER) variants emerged. All ER variants were negative for T790M. RNA from parental and ER cells was isolated for transcriptomic profiling. RNA-seq analysis reveals that EGFR TKI resistance is associated with a mesenchymal gene expression signature.
2020-09-03 | GSE121634 | GEO
Project description:Bidkhori2012 - EGFR signalling in NSCLC
The paper describes and compares two models on EGFR signalling between normal and NSCLC cells. Moreover, it is shown that ERK (MAPK), STAT and Akt factor's activation pattern are different between normal and NSCLA models. This model corresponds to EGFR signalling in NSCLA cells.
Created by The MathWorks, Inc. SimBiology tool, Version 3.3
This model is described in the article:
Modeling of tumor progression in NSCLC and intrinsic resistance to TKI in loss of PTEN expression.
Bidkhori G, Moeini A, Masoudi-Nejad A
PloS one [2012, 7(10):e48004]
Abstract:
EGFR signaling plays a very important role in NSCLC. It activates Ras/ERK, PI3K/Akt and STAT activation pathways. These are the main pathways for cell proliferation and survival. We have developed two mathematical models to relate to the different EGFR signaling in NSCLC and normal cells in the presence or absence of EGFR and PTEN mutations. The dynamics of downstream signaling pathways vary in the disease state and activation of some factors can be indicative of drug resistance. Our simulation denotes the effect of EGFR mutations and increased expression of certain factors in NSCLC EGFR signaling on each of the three pathways where levels of pERK, pSTAT and pAkt are increased. Over activation of ERK, Akt and STAT3 which are the main cell proliferation and survival factors act as promoting factors for tumor progression in NSCLC. In case of loss of PTEN, Akt activity level is considerably increased. Our simulation results show that in the presence of erlotinib, downstream factors i.e. pAkt, pSTAT3 and pERK are inhibited. However, in case of loss of PTEN expression in the presence of erlotinib, pAkt level would not decrease which demonstrates that these cells are resistant to erlotinib.
This model is hosted on BioModels Database
and identified
by: MODEL1304020001
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000453 | BioModels
Project description:In this study, to investigate the underlying molecular mechanisms of how EGFR-TKIs resistance occurs in NSCLC, we examined gene expression using microarray technology on gefitinib-resistant NSCLC cells to obtain differentially expressed (DE) lncRNAs and mRNAs. Then we carried out KEGG enrichment analysis for DE-mRNAs and constructed the ceRNA regulatory network of DE-lncRNAs and DE-mRNAs. Our results revealed the downregulated lncRNA LINC01128 acted as ceRNA to decrease PTEN via sponging miR-25-3p, and then the signal reactions caused by the reduction of PTEN would activate PI3K/Akt signaling pathway, which may lead to the development of drug resistance to EGFR-TKIs in NSCLC. Our findings will provide a novel perspective for the underlying molecular mechanisms of EGFR-TKIs resistance in NSCLC. Besides, this research will help to develop new therapeutic targets for EGFR-TKIs resistance in NSCLC.
2022-01-14 | GSE193628 | GEO