Identification of microRNA differentially expressed in three subtypes of non-small cell lung cancer and in silico functional analysis

Abstract

Emerging studies demonstrated that miRNAs played fundamental roles in lung cancer. In this study, we attempted to explore the clinical significance of the miRNA signature in different histological subtypes of non-small cell lung cancer (NSCLC). Three miRNome profiling datasets (GSE19945, GSE25508 and GSE51853) containing lung squamous cell carcinoma (SCC), lung adenocarcinoma (ADC) and large cell lung cancer (LCLC) samples were obtained for bioinformatics and survival analysis. Moreover, pathway enrichment and coexpression network were performed to explore underlying molecular mechanism. MicroRNA-375 (miR-375), miR-203 and miR-205 were identified as differentially expressed miRNAs (DEmiRNAs) which distinguished SCC from other NSCLC subtypes. Pathway enrichment analysis suggested that Hippo signaling pathway was combinatorically affected by above mentioned three miRNAs. Coexpression analysis of three miRNAs and the Hippo signaling pathway related genes were conducted based on another dataset, GSE51852. Four hub genes (TP63, RERE, TJP1 and YWHAE) were identified as the candidate targets of three miRNAs, and three of them (TP63, TJP1 and YWHAE) were validated to be downregulated by miR-203 and miR-375, respectively. Finally, survival analysis further suggested the prognostic value of three-miRNA signature in SCC patients. Taken together, our study compared the miRNA profiles among three histological subtypes of NSCLC, and suggested that a three-miRNA signature might be potential diagnostic and prognostic biomarkers for SCC patients.