GSE110907
Identification of tumor suppressor microRNAs by integrative miRNA and mRNA sequencing of matched tumor normal pairs in lung adenocarcinoma
Roles of microRNAs (miRNAs) have not yet been explored systematically at the genome scale in lung cancer biology despite their important regulatory functions. Here, we report an integrative analysis of microRNA and mRNA sequencing data for the matched tumor and normal samples from 109 Korean female patients with non-small-cell lung adenocarcinoma. We produced miRNA-Seq and RNA-Seq data for 48 patients and RNA-Seq data only for additional 61 patients. Differential expression analysis with stringent criteria yielded 44 miRNAs and 2,322 genes. Integrative gene set analysis of differentially expressed miRNAs and genes using miRNA-target information yielded several processes related to cell cycle regulation that were targeted by tumor suppressor miRNAs. We performed the colony formation assay in A549 and NCI-H460 cell lines to test the tumor suppressive activity of down-regulated miRNAs in cancer and identified 7 novel tumor suppressor miRNAs. Two miRNAs showed differential survival characteristics in the TCGA LUAD patient cohort, suggesting their prognostic value. Our study not only provides a massive dataset of miRNA and mRNA sequencing from the matched tumor-normal samples but also reports several novel tumor suppressor miRNAs that could be further developed into prognostic biomarkers or RNA therapeutic targets. Overall design: We produced miRNA-Seq in 48 patient-matched lung adenocarcinoma and non-malignant lung tissue pairs from current and never smokers.