Project description:To elucidate the mechanisms by which Nrf2 regulates cell growth, we performed global gene expression profiling of A549 lung cancer cells with knockdown of Nrf2. Gene networks associated with carbohydrate metabolism and drug metabolism were significantly downregulated in Nrf2-depleted A549 cells. Gene Set Enrichment Analysis revealed significant enrichment of genes associated with carbohydrate catabolic processes, positive regulation of metabolic processes, PPP, and arachidonic acid metabolism. In summary, this analysis revealed that Nrf2 positively regulates transcription of genes that play key roles in central carbon metabolism. A549 cells were transfected with non targeting NS siRNA or siRNA targeting Nrf2. Mock transfected A549 cells were treated with transfection reagent alone. We had 3 biological replicates for each of the 3 groups. Ninty six hours post transfection, cells were lysed and total RNA was isolated.
Project description:To identify genes regulated by NFE2L2 (Nrf2), we selected a lung cancer cell line (A549) in which NFE2L2 is normally active. Three transfections using siRNAs targeting NFE2L2 and four control transfections using two different negative control siRNAs were done. As a result, we found several genes up or down regulated in response to NFE2L2 inactivation in these cells.
Project description:This study aimed to elucidate the relationships between NRF2 and disease progression and provide insight into NRF2-mediated cancer progression/tumorigenesis by identifying novel genes and pathways regulated by NRF2 in A549 NSCLC cells
Project description:To elucidate the mechanisms by which Nrf2 regulates cell growth, we performed global gene expression profiling of A549 lung cancer cells with knockdown of Nrf2. Gene networks associated with carbohydrate metabolism and drug metabolism were significantly downregulated in Nrf2-depleted A549 cells. Gene Set Enrichment Analysis revealed significant enrichment of genes associated with carbohydrate catabolic processes, positive regulation of metabolic processes, PPP, and arachidonic acid metabolism. In summary, this analysis revealed that Nrf2 positively regulates transcription of genes that play key roles in central carbon metabolism.
Project description:Resveratrol, a natural phytoestrogen found in red wine and a variety of plants, is reported to have protective effects against lung cancer, however there is very little work directed towards the understanding of the mechanism of action of resveratrol in lung cancer. In this study we used an experimental approach to understand the biological activity and molecular mechanisms of resveratrol in A549 lung cancer cells. Gene expression profiles were compiled using an oligonucleotide microarray to determine altered expression levels in resveratrol treated cells. Keywords: Genetic modification of A549 cells in response to resveratrol
Project description:NEDD9 is important for lung cancer metastasis. However, the detailed mechanism remains elusive. Using the microarray data generated with human lung cancer cell lines with either NEDD9 overexpression or NEDD9 knockdown, we plan to idnetify important signal pathways regulated by NEDD9. This may explain how NEDD9 excutes its function in lung cancer. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. Human lung cancer cell line A549, which has LKB1 loss-of-function mutation and increased expression of NEDD9, was used for two individual NEDD9 knockdown. Human lung cancer cell line CRL-5907, which has wild-type LKB1 and low NEDD9 expression level, was used for NEDD9 overexpression. The microarray was done in A549 cells, A549 cells with two different NEDD9 knockdown; CRL-5907 cells and CRL-5907 cells with NEDD9 overexpression.
Project description:We identified RNA binding motif protein 47 (RBM47) as a target gene of transforming growth factor (TGF)-beta in mammary gland epithelial cells (NMuMG cells) that have undergone the epithelial-to-mesenchymal transition (EMT). TGF-beta repressed RBM47 expression in NMuMG cells and lung cancer cell lines. Expression of RBM47 correlated with good prognosis in patients with lung, breast, and gastric cancer. RBM47 suppressed the expression of cell metabolism-related genes, which were the direct targets of nuclear factor erythroid 2-related factor 2 (Nrf2; also known as NFE2L2). RBM47 bound to KEAP1 and Cullin3 mRNAs, and knockdown of RBM47 inhibited their protein expression, which led to enhanced binding of Nrf2 to target genomic regions. Knockdown of RBM47 also enhanced the expression of some Nrf2 activators, p21/CDKN1A and MafK induced by TGF-beta. Both mitochondrial respiration rates and the side population cells in lung cancer cells increased in the absence of RBM47. Our findings, together with the enhanced tumor formation and metastasis of xenografted mice by knockdown of the RBM47 expression, suggested tumor suppressive roles for RBM47 through the inhibition of Nrf2 activity. Effect of shRNA for RBM47 and TGF-beta on gene expression was evaluated by RNA-seq and RBM47-bound RNAs were identified by RIP-seq in A549 cells.