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Background Aberrant miRNA expression and DNA methylation are two major epigenetic events in lung adenocarcinoma (LUAD). We conducted a combined analysis of the molecular changes in LUAD. Methods We analyzed differentially expressed miRNAs and methylated CpG loci in 489 LUAD tissues versus 49 normal lung tissues of the Cancer Genome Atlas (TCGA). The results were validated in cell lines and xenograft mouse models and additional pairs of 36 LUAD and 36 normal lung tissues. Results A total of 125 differentially expressed miRNAs and 145 dif