3' UTR RNA-sequencing of human EGFR-mutant lung adenocarcinoma cell lines treated with trametinib or controls
Ontology highlight
ABSTRACT: Human EGFR-mutated lung adenocarcinoma cell lines HCC4006, HCC827 and PC9 were treated with trametinib or DMSO to assess the impact on transcription.
Project description:Lung adenocarcinoma PC9 cells were engineered to not only contain the driving EGFR-mutations, but also EGFR T790M and EGFR C797S that provide resistance to EGFR inhibitors.
Project description:Human EGFR-mutant lung adenocarcinoma cells (PC9) were engineered using CRISPRv2 systemt to knock-out MAVS or STING to assess impact on transcriptomic response following osimertinib treatment
Project description:In the human EGFR mutant adenocarcinoma cell line PC9 pBabe empty vector (EV) or BRAF V600E were overexpressed. RNA was extracted from EV, BRAF V600E overexpressing or osimertinib-resistant BRAF V600E expressing cells after 48h treatment with osimertinib, trametinib, a combination of both or vehicle controls. RNA was subjected to 3' UTR RNA sequencing.
Project description:Human EGFR-mutant lung cancer cells lines were investigated for their dynamic transcriptional response upon treatment with EGFR-inhibitor osimertinib in a time-series experiment
Project description:Drug tolerant persister cells of EGFR-mutant PC9 cell lines surviving treatment with kinase inhibitor combination. Cells were treated with combination of erlotinib, osimertinib, trametinib and dasatinib and surviving cells were harvested for RNA extraction. 3' UTR RNA-seq profiles were compared to parental control cells and to outgrowing cells after treatment had been removed
Project description:The transcriptomic effects of EGFR-inhibition by osimertinib on murine EGFR-mutant lung cancer transplants in a syngenic model were assessed.
Project description:EGFR-mutant lung adenocarcnioma cell line PC9 pools were treated with different compounds until resistant cells regrew. Resistant and parental cells were then sequenced to study transcriptional changes.
Project description:Immunocompromised mice were inoculated with human lung adenocarcinoma cell line PC9 and with human PBMCs. Tumors were treated with osimertinib/vehicle of RIG-I agonist IVT4/unspecific control IVT-GAC to assess response.
Project description:Purpose: Multiple mechanims have been proposed that lead to reduced effectiveness of EGFR tyrosine kinase inhibitors (TKIs) in lung cancer and yet resistance to osimertinib and gefitinib still remains a challenge in the clinic. The goals of this study are to identify key genes contributing to tolerance and resistance to EGFR inhibition. Methods: mRNA profiles of gefitinib and osimertinib tolerant cells in PC9 and HCC827 cells were generated by deep sequencing using Illumina. In addition, mRNA profiles of cells (AALE, PC9 and HCC827) overexpressing with miR-147b or miR-21 and mRNA profiles of cells (H1975 and PC9ER) with miR-147b and miR-21 knocking down were generated by deep sequencing. The mappable reads were aligned to the human transcripts using Bowtie2 and gene abundance was estimated using RSEM. Results: Upregulation of miR-147b and miR-21 expression is related to tolerance and resistance to gefitinib and osimertinib in lung cancer. The signaling pathways of transcripts by knocking down miR-147b or miR-21 in resistant cells (H1975 and PC9ER) and by overexpressing miR-147b or miR-21 in both sensistive cells (HCC827 and PC9) and immortalized lung epithelial cells (AALE) are consistent with the key signaling pathways shown in tolerant cells to gefitinib and osimertinib in HCC827 and PC9 cells (HCC827GTR/OTR vs HCC827 and PC9GTR/OTR vs PC9). Conclusions: Our work identifies key signaling pathways that mediate EGFR-TKI tolerance and resistance in lung cancer. Our study provides potential targets to improve the efficacy of EGFR-TKIs therapy in cancer pagtients.
Project description:Patient derived xenografts (PDXs) of human EGFR-mutant lung cancer were propagated in mice and treated with osimertinib or control to investigate the transcriptional adaption resposne.