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Gene expression signatures affected by ethanol and/or nicotine in normal human normal oral keratinocytes (NHOKs).

ABSTRACT: It has been reported that nicotine/alcohol alter epigenetic control and lead to abrogated DNA methylation and histone modifications, which could subsequently perturb transcriptional regulation critically important in cellular transformation. The aim of this study is to determine the molecular mechanisms of nicotine/alcohol-induced epigenetic alterations and their mechanistic roles in transcriptional regulation in human adult stem cells. We hypothesized that nicotine/alcohol induces deregulation of epigenetic machinery and leads to epigenetic alterations, which subsequently affect transcriptional regulation in oral epithelial stem cells. As an initiating step we have profiled transcriptomic alterations induced by combinatory administration of EtOH and nicotine in primary normal human oral keratinocytes. Here we provide detailed experimental methods, analysis and information associated with our data deposited into Gene Expression Omnibus (GEO) under GSE57634. Our data provide comprehensive transcriptomic map describing molecular changes induced by EtOH and nicotine on normal human oral keratinocytes.

SUBMITTER: Kim JJ

PROVIDER: S-EPMC4127651 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Gene expression signatures affected by ethanol and/or nicotine in normal human normal oral keratinocytes (NHOKs).

Kim Jeffrey J JJ Khalid Omar O Duan Lewei L Kim Reuben R Elashoff David D Kim Yong Y

Genomics data 20141201

It has been reported that nicotine/alcohol alter epigenetic control and lead to abrogated DNA methylation and histone modifications, which could subsequently perturb transcriptional regulation critically important in cellular transformation. The aim of this study is to determine the molecular mechanisms of nicotine/alcohol-induced epigenetic alterations and their mechanistic roles in transcriptional regulation in human adult stem cells. We hypothesized that nicotine/alcohol induces deregulation ...[more]

PMID: 25126520

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Project description:BackgroundSince the first evidence suggesting existence of stem-like cancer cells, the process of cells reprogramming to the stem cell state remains as an attractive tool for cancer stemness research. Current knowledge in the field of cancer stemness, indicates that the microenvironment is a fundamental regulator of cell behavior. With regard to this, we investigated the changes of genome wide gene expression in reprogrammed human colon normal epithelial CRL-1831 and colon carcinoma DLD1 cell lines grown under more physiologically relevant three-dimensional (3D) cell culture microenvironment compared to 2D monolayer.MethodsWhole genome gene expression changes were evaluated in both cell lines cultured under 3D conditions over a 2D monolayer by gene expression microarray analysis. To evaluate the biological significance of gene expression changes, we performed pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Gene network analysis was used to study relationships between differentially expressed genes (DEGs) in functional categories by the GeneMANIA Cytoscape toolkit.ResultsIn total, we identified 3228 and 2654 differentially expressed genes (DEGs) for colon normal and cancer reprogrammed cell lines, respectively. Furthermore, the expression of 1097 genes was commonly regulated in both cell lines. KEGG enrichment analysis revealed that in total 129 and 101 pathways for iPSC-CRL-1831 and for CSC-DLD1, respectively, were enriched. Next, we grouped these pathways into three functional categories: cancer transformation/metastasis, cell interaction, and stemness. β-catenin (CTNNB1) was confirmed as a hub gene of all three functional categories.ConclusionsOur present findings suggest common pathways between reprogrammed human colon normal epithelium (iPSC-CRL-1831) and adenocarcinoma (CSC-DLD1) cells grown under 3D microenvironment. In addition, we demonstrated that pathways important for cancer transformation and tumor metastatic activity are altered both in normal and cancer stem-like cells during the transfer from 2D to 3D culture conditions. Thus, we indicate the potential of cell culture models enriched in normal and cancer stem-like cells for the identification of new therapeutic targets in cancer treatment.

Dataset Information

Gene expression signatures affected by ethanol and/or nicotine in normal human normal oral keratinocytes (NHOKs).

Publications

Gene expression signatures affected by ethanol and/or nicotine in normal human normal oral keratinocytes (NHOKs).

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