The role of miR-130a-3p and SPOCK1 in tobacco exposed bronchial epithelial BEAS-2B transformed cells: Comparison to A549 and H1299 lung cancer cell lines

Abstract

ABSTRACTIn the pathogenesis of human lung cancer induced by tobacco smoke decreased expression levels of microRNAs (miRNAs) are known to occur. At present, the specific miRNAs expression levels reduced by tobacco smoke and subsequent lung cellular transformation remain to be determined. The aim of this study was thus to identify the miRNAs affected following cigarette-smoke exposure in bronchial epithelial BEAS-2B cells that were malignantly transformed into S30 cells. In addition, the miRNAs in S30 transformed cells were compared to human lung cancer cell lines A549 and H1299. Our results identified miR-130a-3p which was down-regulated in S30 cells as well as A549 and H1299 lung cancer cell lines. Using miRNA mimic, a correlation between elevated miR-130a-3p expression levels and reduced migration in A549 and H1299 cell lines and S30 cells was noted as evidenced by transwell and wound healing assays accompanied by enhanced apoptosis. Further, two online target genes prediction programs TargetScan and miRDB were employed to identify the miRNA target gene SPOCK1 in all three cell types. SPOCK1 expression was higher in unexposed bronchial epithelial BEAS-2B cells. It is of interest that however silencing SPOCK1 in transformed S30 cells exposed to cigarette-smoke a marked depression in cell migration was noted. Our findings demonstrate that upregulated miR-130a-3p was associated with reduced SPOCK1 expression in transformed S30 as well as lung cancer A549 and H1299 cell lines indicating that cigarette transformed cells behave similar to lung cancer cells and this process involves diminished lung cancer cells migration.