Lung cancer and miRNAs: a possible remedy for anti-metastatic, therapeutic and diagnostic applications

Abstract

Abstract Background Lung cancer is often diagnosed as stage IV metastatic disease and is the leading cause of cancer-related death worldwide. Expression of micro-ribonucleic acids (microRNAs, miRNAs) and long-noncoding RNAs (lncRNAs) has been associated with metastasis in various tumor types. The present study investigates the role of miRNA and lncRNA in metastatic lung cancer. Methods We analyzed seven microarray chips from the Gene Expression Omnibus (GEO) database including 135 lung cancer samples with miRNA, lncRNA, or mRNA to identify differentially expressed molecules in primary versus metastatic lung cancer. The clinical relevance of identified molecules was confirmed by examining clinical data from 32 patients with metastatic lung cancer in The Cancer Genome Atlas (TCGA) dataset. Co-expression and protein-protein-interaction (PPI) patterns were analyzed to identify candidate hub genes. Tumor immune infiltrate was analyzed to determine potential mechanisms of the hub genes. Results We identified 15 miRNAs (miR-483-3p, miR-519-b-5p, miR-519c-5p, miR-586, miR-647, miR-875-3p, miR-137, miR-924, miR-922, miR-199b-5p, miR-610, miR-519c-3p, miR-548m, miR-384, miR-1289) and 6 target genes (SORBS1, GAB1, RPS6KA2, KIT, LRCH2, and PECAM1) with differential expression in primary versus metastatic disease. In addition, we identified 105 lncRNAs that were associated with metastatic lung cancer. The PPI network predicted 14 transcription factors that were likely to be involved the development of metastatic lung cancer, and analysis of the immune infiltrate showed that hub genes in the PPI network may alter the tumor immune microenvironment to drive metastatic progression. Conclusions We identified key molecules that form a functional network to regulate the development and progression of metastatic lung cancer that may be promising new targets to treat this lethal disease.