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Plos One : an Integrated Expression Profiling Reveals Target Genes of Tgf-b and Tnf-a Possibly Mediated by Micrornas in Lung Cancer Cells, Volume 7

By Kalinichenko, Vladimir, V.

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Book Id: WPLBN0003933733
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos One : an Integrated Expression Profiling Reveals Target Genes of Tgf-b and Tnf-a Possibly Mediated by Micrornas in Lung Cancer Cells, Volume 7  
Author: Kalinichenko, Vladimir, V.
Volume: Volume 7
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection (Contemporary)
Historic
Publication Date:
Publisher: Plos

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Kalinichenko, V. V. (n.d.). Plos One : an Integrated Expression Profiling Reveals Target Genes of Tgf-b and Tnf-a Possibly Mediated by Micrornas in Lung Cancer Cells, Volume 7. Retrieved from http://worldebookfair.com/


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Description : EMT (epithelial-mesenchymal transition) is crucial for cancer cells to acquire invasive phenotypes. In A549 lung adenocarcinoma cells, TGF-b elicited EMT in Smad-dependent manner and TNF-a accelerated this process, as confirmed by cell morphology, expression of EMT markers, capacity of gelatin lysis and cell invasion. TNF-a stimulated the phosphorylation of Smad2 linker region, and this effect was attenuated by inhibiting MEK or JNK pathway. Comprehensive expression analysis unraveled genes differentially regulated by TGF-b and TNF-a, such as cytokines, chemokines, growth factors and ECM (extracellular matrices), suggesting the drastic change in autocrine/paracrine signals as well as cell-to-ECM interactions. Integrated analysis of microRNA signature enabled us to identify a subset of genes, potentially regulated by microRNAs. Among them, we confirmed TGF-b-mediated induction of miR-23a in lung epithelial cell lines, target genes of which were further identified by gene expression profiling. Combined with in silico approaches, we determined HMGN2 as a downstream target of miR-23a. These findings provide a line of evidence that the effects of TGF-b and TNF-a were partially mediated by microRNAs, and shed light on the complexity of molecular events elicited by TGF-b and TNF-a.

 

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