Gene expression profiling associated with knockdown of RNF20 in human normal and malignant lung epithelial cell lines
Ontology highlight
ABSTRACT: The experiment was designed to display differential gene expression profiling in one lung epithelial cell BEAS2-B, and three lung cancer cell lines A549, H1299, H460 cells upon knockdown of RNF20, by using RNAseq technology.
Project description:The experiment was designed to display differential gene expression profiling changes in two human non-small cell lung cancer cells A549 and H1299 upon knockout of USP22 gene, by using RNAseq technology.
Project description:Defective DNA repair and metabolic rewiring are highly intertwined in promoting the development and progression of cancer. However, the molecular players at the interface of these processes remain largely unexplored. Here we show that the Rnf20-HIF1α axis links the DNA damage response and metabolic reprogramming in lung cancer. Haploinsufficiency of Rnf20 which catalyzes monoubiquitylation of histone H2B (H2Bub1), dramatically increased the incidence of spontaneous lung adenocarcinoma and small cell lung cancer (SCLC) in mice. Mechanistically, ablation of a single Rnf20 allele resulted in inadequate tumor suppression via the Rnf20-H2Bub1-p53 axis and induced DNA damage, increased cell growth, epithelial-mesenchymal transition (EMT), and metabolic rewiring through HIF1α-mediated RNA polymerase II promoter-proximal pause release, that was independent of H2Bub1. Importantly, RNF20 levels are reduced in lung adenocarcinoma and SCLC patients, and this reduction negatively correlates with the expression of HIF1α target genes, suggesting HIF1α inhibition as a promising therapeutic approach for lung cancer patients with reduced RNF20 activity
Project description:Defective DNA repair and metabolic rewiring are highly intertwined in promoting the development and progression of cancer. However, the molecular players at the interface of these processes remain largely unexplored. Here we show that the Rnf20-HIF1α axis links the DNA damage response and metabolic reprogramming in lung cancer. Haploinsufficiency of Rnf20, catalyzing histone H2B monoubiquitylation (H2Bub1), dramatically increases the occurrence of spontaneous lung adenocarcinoma and small cell lung carcinoma (SCLC) in mice. Mechanistically, ablation of a single Rnf20 allele resulted in insufficient Rnf20-H2Bub1-p53-mediated control and induced pronounced defects in DNA repair, increased cell growth, epithelial-to-mesenchymal transition (EMT), and metabolic rewiring via HIF1α-mediated RNA polymerase II promoter-proximal pause release, which was independent of H2Bub1. Importantly, RNF20 levels are decreased in lung adenocarcinoma and SCLC patients, and this decrease negatively correlates with the expression of HIF1α target genes, suggesting HIF1α inhibition as a promising therapeutic approach for lung cancer patients with decreased RNF20 activity.
Project description:Defective DNA repair and metabolic rewiring are highly intertwined in promoting the development and progression of cancer. However, the molecular players at the interface of these processes remain largely unexplored. Here we show that the Rnf20-HIF1α axis links the DNA damage response and metabolic reprogramming in lung cancer. Haploinsufficiency of Rnf20, catalyzing histone H2B monoubiquitylation (H2Bub1), dramatically increases the occurrence of spontaneous lung adenocarcinoma and small cell lung carcinoma (SCLC) in mice. Mechanistically, ablation of a single Rnf20 allele resulted in insufficient Rnf20-H2Bub1-p53-mediated control and induced pronounced defects in DNA repair, increased cell growth, epithelial-to-mesenchymal transition (EMT), and metabolic rewiring via HIF1α-mediated RNA polymerase II promoter-proximal pause release, which was independent of H2Bub1. Importantly, RNF20 levels are decreased in lung adenocarcinoma and SCLC patients, and this decrease negatively correlates with the expression of HIF1α target genes, suggesting HIF1α inhibition as a promising therapeutic approach for lung cancer patients with decreased RNF20 activity.
Project description:Defective DNA repair and metabolic rewiring are highly intertwined in promoting the development and progression of cancer. However, the molecular players at the interface of these processes remain largely unexplored. Here we show that the Rnf20-HIF1α axis links the DNA damage response and metabolic reprogramming in lung cancer. Haploinsufficiency of Rnf20, catalyzing histone H2B monoubiquitylation (H2Bub1), dramatically increases the occurrence of spontaneous lung adenocarcinoma and small cell lung carcinoma (SCLC) in mice. Mechanistically, ablation of a single Rnf20 allele resulted in insufficient Rnf20-H2Bub1-p53-mediated control and induced pronounced defects in DNA repair, increased cell growth, epithelial-to-mesenchymal transition (EMT), and metabolic rewiring via HIF1α-mediated RNA polymerase II promoter-proximal pause release, which was independent of H2Bub1. Importantly, RNF20 levels are decreased in lung adenocarcinoma and SCLC patients, and this decrease negatively correlates with the expression of HIF1α target genes, suggesting HIF1α inhibition as a promising therapeutic approach for lung cancer patients with decreased RNF20 activity.
Project description:Defective DNA repair and metabolic rewiring are highly intertwined in promoting the development and progression of cancer. However, the molecular players at the interface of these processes remain largely unexplored. Here we show that the Rnf20-HIF1α axis links the DNA damage response and metabolic reprogramming in lung cancer. Haploinsufficiency of Rnf20, catalyzing histone H2B monoubiquitylation (H2Bub1), dramatically increases the occurrence of spontaneous lung adenocarcinoma and small cell lung carcinoma (SCLC) in mice. Mechanistically, ablation of a single Rnf20 allele resulted in insufficient Rnf20-H2Bub1-p53-mediated control and induced pronounced defects in DNA repair, increased cell growth, epithelial-to-mesenchymal transition (EMT), and metabolic rewiring via HIF1α-mediated RNA polymerase II promoter-proximal pause release, which was independent of H2Bub1. Importantly, RNF20 levels are decreased in lung adenocarcinoma and SCLC patients, and this decrease negatively correlates with the expression of HIF1α target genes, suggesting HIF1α inhibition as a promising therapeutic approach for lung cancer patients with decreased RNF20 activity.
Project description:The protein(s) larger than 100 kDa in conditioned medium from lung cancer cell lines activated microglia. The >100 kDa fraction of conditioned medium from H460, H1299, H2030, or H292 cells was collected. Proteins present in the conditioned medium were analyzed by LC-MS/MS.
Project description:To examine the effect of metformin on lung cancer biology, human lung A549 adenocarcinoma, H460 large cell carcinoma, and H226 and H1299 squamous cell carcinoma cell-lines were grown in RPMI-1640 medium with 10% v/v fetal bovine serum and with or without 15 uM metformin hydrochloride for 7-8 days. Medium (with any metformin) was replaced every two days. Paired cultures with and without metformin were grown and maintained in parallel. Three separate paired cultures, all seeded with same stock of frozen cells, were grown. Cells, within 15%-95% confluence range, were harvested by scraping. Total RNA from cells was prepared using Norgen Biotek® Total RNA Isolation kit (with on-column DNAse I treatment). All RNA integrity number (RIN) values were greater than 8.2.
Project description:To identify a set of genes related to radioresistance, we analyzed the time-series gene expression profiles of radioresistant H1299 and radiosensitive H460 lung cancer cells in response to 2 Gy of ionizing radiation (IR) by performing quadratic regression (QR) analysis. Out of the 21,331 genes, we selected 6,538 genes by QR analysis from the gene expression profile of H460 cells and 6,086 genes from that of H1299 cells. Most of the genes identified in the H460 cells were classified into continuously up- or down-regulated groups, while the major QR groups were transiently changed groups in the H1299 cell line. From gene ontology analysis of the major QR groups, the DNA damage response was commonly enriched in both cell lines. DNA repair-related genes such as ATM, ATR, TP53BP1, BRCA1, MRE11, NBN and RAD50 were particularly up-regulated in H1299 cells. Suppression of these DNA repair-related genes using siRNA made H1299 cells radiosensitive to ionizing radiation. The data suggest that differential responses to DNA damage confer radioresistance to cancer cells, and provide potential novel targets for sensitizing radiotherapy.
Project description:We report the gene expression profiles by NGFR knockdown in H460 and H1299 cell lines and reveal that NGFR ablation activates p53 target gene expression. We examined gene expression in two different non-small-cell lung cancer cell lines, one with wild-type p53 and the other without p53.