Gene expression in an EMT model using an immortalized bronchial epithelial cell line induced by TGF-β1
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE40374 | GEO | 2013/10/06
SECONDARY ACCESSION(S): PRJNA173793
REPOSITORIES: GEO
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Project description:This study aimed to establish an epithelial-mesenchymal transition (EMT) model with an immortalized human bronchial epithelial cell line, M-BE, and to identify an EMT signature gene set. The TGF-M-NM-21-induced M-BE cells got spindle-shaped fibroblast-like morphology and lost the cell-cell contact, with down-regulated expression of epithelial marker E-cadherin and up-regulated expression of mesenchymal markers N-cadherin and Vimentin. Examined by microarray, there were 2628 genes identified as significant EMT-related, including 1490 up-regulated genes (FC > 2, fdr < 0.01) and 1138 down-regulated genes (FC < 0.5, fdr < 0.01) in TGF-M-NM-21-induced M-BE cells. M-BE cells were treated with human recombinant TGF-M-NM-21 (5ng/ml) for six days. M-BE cells cultured without TGF-M-NM-21 were considered the controls. Three replicates of each were carried out for this investigation. Agilent 4x44K Human Whole Genome expression microarray (G4112F) analysis was applied to the RNA samples of the TGF-M-NM-21-treated M-BE cells and the controls.
2013-10-06 | E-GEOD-40374 | biostudies-arrayexpress
Project description:Long noncoding RNAs (lncRNAs) are emerging as important regulators in cellular processes. In the present study, the effects of the long non-coding RNA, SNHG5 was investigated in lung adenocarcinoma (LAD) and we also revealed the underlying mechanisms of it. Overexpressed SNHG5 suppressed migration and invasion of LAD cell line A549 in vitro. Transcriptome sequencing analysis supported the inhibitory effects of SNHG5 were associated with cell adhesion molecules. In addition, western blot and immunofluorescence showed that the expression of SNHG5 was associated with epithelial-mesenchymal transition (EMT) markers. Furthermore, we determined the effects of SNHG5 in EMT procession of A549 induced by TGF-β1. Consistent with previous results, overexpression of SNHG5 suppressed the migration and invasion, and also the expression of EMT-related transcription factors including Snail, SLUG and ZEB1 in EMT of A549 reduced by TGF-β1. Moreover, qRT-PCR demonstrated expression of SNHG5 was positively correlated with E-cadherin protein expression, but negatively correlated with N-cadherin and Vimentin in LAD tissues. In summary, our study demonstrated that lncRNA SNHG5 could suppress cell migration and invasion of LAD cancer by inhibiting EMT procession, highlighting the potential of SNHG5 as a therapy strategy for lung adenocarcinoma.
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Project description:Recently, we found that a novel Traf2- and Nck-interacting kinase (TNIK) inhibitor, named NCB-0846, was capable of attenuating tumor-initiating cells among human colorectal cancer. The cross link between EMT and cancer stemness has been revealed in several studies and other group showed another TNIK inhibitor named KY-05009 had inhibited the TGF-β-induced EMT. Therefore we evaluated whether this small-molecule compound could have efficacy to inhibit TGF-β-induced EMT. NCB-0846 reduced the expression of mesenchymal markers (Vimentin and N-cadherin) and upregulated the expression of epithelial marker E-cadherin in A549 and H2228 non-small cell lung cancer cells. NCB-0846 suppressed the phosphorylation and nuclear translocation of Smad proteins and also inhibited migration, invasion, and metastasis. NCB-0846 inhibited TGF-β1-induced EMT through the down-regulation of TGF-β receptor-1 (TβRI) in mRNA levels. MiR-186-5p and miR-320 family were identified as candidate miRNAs that could target TβRI and we found that miR-186-5p and miR-320s inhibited TβRI expression. NCB-0846 might be a novel therapeutics drugs that targets the invasion and metastasis through inhibiting TGF-β-induced EMT in lung cancer.
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Project description:Microarray analysis reveals up-regulation of retinoic acid and hepatocyte growth factor related signaling pathways by pro-insulin C-peptide in kidney proximal tubular cells: Antagonism of the pro-fibrotic effects of TGF-b1 Novel signaling roles for C-peptide have recently been discovered with evidence that it can ameliorate complications of type 1 diabetes. Here we sought to identify new pathways regulated by C-peptide of relevance to the pathophysiology of diabetic nephropathy. Microarray analysis was performed to identify genes regulated by either C-peptide and/or transforming growth factor beta 1 (TGF-β1) in a human proximal tubular cell line, HK-2. Expression of retinoic acid receptor β (RARβ), hepatcoyte growth factor (HGF), cellular retinoic acid binding protein II (CRABPII), vimentin, E-cadherin, Snail and β-catenin was assessed by immunoblotting. The cellular localisation of vimentin and β-catenin was determined by immunocytochemistry. Changes in cell morphology were assessed by phase contrast microscopy. Gene expression profiling demonstrated differential expression of 953 and 1,458 genes after C-peptide exposure for 18h or 48h respectively. From these, members of the anti-fibrotic retinoic acid (RA) and HGF signaling pathways were selected. Immunoblotting demonstrated that C-peptide increased RARβ, CRABPII and HGF. We confirmed a role for RA in reversal of TGF-β1-induced changes associated with epithelial-mesenchymal transition (EMT), including expression changes in Snail, E-cadherin, vimetin and redistribution of β-catenin. Importantly, these TGF-β1-induced changes were inhibited by C-peptide. Further, effects of TGF-β1 on Snail and E-cadherin expression were blocked by HGF and inhibitory effects of C-peptide were removed by blockade of HGF activity. This study identifies a novel role for HGF as an effector of C-peptide, possibly via an RA signaling pathway, highlighting C-peptide as a potential therapy for diabetic nephropathy.
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Project description:Vicious circle of some key proteins is critical in the process of tumor development. Nevertheless, the mechanism of how the epigenetic modifiers are involved in was seldom reported and has not been clearly illustrated. We found the expression of lysine specific demethylase 1 (LSD1), the first identified histone lysine demethylase, is positively correlated with transforming growth factor beta 1 (TGF β1) in gastric cancer tissues and can be promoted by TGF β1 activated (p-EKR)-(NF-κB)-p300 signaling pathway, which resulted in the progression of epithelial-mesenchymal transition (EMT) in human gastric cancer cells. On the other hand, abrogation of LSD1 leads to the down regulation of TGF β1 as well as the EMT. But in benign cells, this circle was blocked by TGF β1 induced inactivation of ERK, which suggested the distinct roles of TGF β1 against LSD1 in gastric cancer cells and benign cells. This vicious cycle may illustrate a novel mechanism for EMT in gastric cancer mediate by TGF β1 and LSD1 but not in benign cells and may serve as a new strategy for the prevention of EMT for gastric cancer.
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