Genome-Wide miRNA Expression Profiling Identifies miR-9-3 and miR-193a as Targets for DNA Methylation in Non–Small Cell Lung Cancers

摘要: Purpose: The major aim of this study was to investigate the role DNA methylation (referred as methylation) on miRNA silencing in non–small cell lung cancers (NSCLC). Experimental Design: We conducted microarray expression analyses 856 miRNAs NSCLC A549 cells before and after treatment with methyltransferase inhibitor 5-aza-2′-deoxycytidine (Aza-dC) a combination Aza-dC histone deacetylase trichostatin A. determined 11 lines primary tumors corresponding nonmalignant tissue samples 101 patients stage I–III NSCLC. Results: By comparing data untreated drug-treated cells, we identified 33 whose upregulated drug which are associated CpG island. Thirty (91%) these were found be methylated at least 1 analyzed. Moreover, miR-9-3 miR-193a tumor specifically observed shorter disease-free survival squamous carcinoma (LSCC) than unmethylated LSCC by multivariate analysis [HR = 3.8; 95% confidence interval (CI), 1.3–11.2, P 0.017] overall univariate ( 0.013). Conclusions: Overall, our results suggest that is an important mechanism for inactivation certain NSCLCs may serve prognostic parameter LSCC. Clin Cancer Res; 18(6); 1619–29. ©2012 AACR .