演講公告
新聞標題: ( 2013-01-14 )
演講主題:From Microarray to Sequencing: Epigenetic alteration of TGF-b targets in ovarian cancer
主講人:陳永恩教授
演講日期:2013年01月15日(二) 10:00-11:30
演講地點:(光復校區) 科學一館307室
摘要內容:
Resistance to TGF-β is frequently observed in ovarian cancer, and disrupted TGF-β/SMAD4 signaling results in aberrant expression of downstream target genes in the disease. We hypothesized that aberrant expression of TGF-b/SMAD4 targets are mediated through epigenetic mechanism and also contribute to resistance to TGF-β meditated growth inhibition. To address this question, we first simultaneously performed chromatin immunoprecipitation followed by microarray analysis (ChIP-chip) and mRNA expression profiling to identify TGF-beta/SMAD regulated and synchronously coexpressed gene sets in ovarian surface epithelium.
Intersecting the ChIP-chip and gene expression data yielded 150 direct targets, of which 141 were grouped into 3 co-expressed gene sets (sustained up-regulated, transient up-regulated and down-regulated), based on their temporal changes in expression after TGF-beta activation. We developed a data-mining method driven by the Random Forest algorithm to model SMAD transcriptional modules in the target sequences.
Subsequent analysis found that some of these SMAD4 targets were epigenetically silenced by promoter hypermethylation in ovarian cancer cells. Methylation of these target genes can predict survival in ovarian cancer patients thus confirming our hypothesis. Recently, the results from microarray were refined by high throughput sequencing technology which will be discussed at the end of the presentation.
