Unknown,Transcriptomics,Genomics,Proteomics

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Promoter context-specific positive and negative transcriptional regulation of Glucocorticoid Receptor target genes by coregulator G9a

ABSTRACT: A549 lung cancer cells were not infected (NI), transfected by plasmids containing shG9a (sequence targeting G9a gene) or shNS (non-specific sequence). These cells were treated with dex to identify subsets of genes regulated by dex (hormone) and G9a (EHMT2) Cells (NI/shNS/shG9a) were treated with 100nM dex for 24h and total RNA was extracted to identify differentially expressed genes

ORGANISM(S): Homo sapiens

SUBMITTER: Dai-Ying Wu

PROVIDER: E-GEOD-35962 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Lung cancer is the leading cause of cancer death worldwide and adenocarcinoma is its most common histological subtype. Clinical and molecular evidence indicates that lung adenocarcinoma is a heterogeneous disease, which has important implications for treatment. Here we performed genome-scale DNA methylation profiling using the Illumina Infinium HumanMethylation27 platform on 59 matched lung adenocarcinoma/non-tumor lung samples, with genome-scale verification on an independent set of tissues. We identified 766 genes showing altered DNA methylation between tumors and non-tumor lung. By integrating DNA methylation and mRNA expression data, we identified 164 hypermethylated genes showing concurrent downregulation, and 57 hypomethylated genes showing increased expression. Integrated pathways analysis indicates that these genes are involved in cell differentiation, epithelial to mesenchymal transition, RAS and WNT signaling pathways and cell cycle regulation, among others. Comparison of DNA methylation profiles between lung adenocarcinomas of current and never-smokers showed modest differences, identifying only LGALS4 as significantly hypermethylated and downregulated in smokers. LGALS4, encoding a galactoside-binding protein involved in cell-cell and cell-matrix interactions, was recently shown to be a tumor-suppressor in colorectal cancer. Unsupervised analysis of the DNA methylation data identified two tumor subgroups, one of which showed increased DNA methylation and was significantly associated with KRAS mutation and to a lesser extent, with smoking. Our analysis lays the groundwork for further molecular studies of lung adenocarcinoma by providing new candidate DNA methylation biomarkers for early detection, identifying novel molecular alterations potentially involved in lung adenocarcinoma development/progression, and describing an epigenetic subgroup of lung adenocarcinoma associated with KRAS mutation. 59 lung adenocarcinoma and 59 adjacent non-tumor lung tissue were macrodissected, bisulfite treated and analyzed on the Illumina Infinium HumanMethylation27K BeadChip

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Promoter context-specific positive and negative transcriptional regulation of Glucocorticoid Receptor target genes by coregulator G9a

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