MicroRNA Expression Profiling of Lung Cancer with Differential Expression of the RON Receptor Tyrosine Kinase

Abstract

Background. The Ron receptor tyrosine kinase (RON) can act as a protooncogene and may play a prominent role in the initiation and development of lung cancer. microRNAs (miRNA) are master regulators of gene expression through direct or indirect regulation, and impact all aspects of cell biology. Methods. Nonsmall-cell lung cancer (NSCLC) samples and small-cell lung cancer (SCLC) were stratified based on RON expression to identify miRNA profiles associated with RON expression levels, differentially expressed miRNA regulated by RON were screened out, and their biological behavior was analyzed. Results. miRNA expression was most significantly affected by cancer type, and we found 85 miRNAs that were significantly differentially expressed between NSCLC and SCLC. There were 46 miRNAs differentially expressed between high RON expressing NSCLC compared to low RON expressing NSCLC. Biological processes and pathways found to be significantly influenced by RON expression included epithelial-mesenchymal transition (EMT) and activation of the PI3K-Akt and MAPK signaling pathways. Conclusions. These data may provide the basis for a novel strategy to characterize lung cancer by RON expression and microRNA genotyping.