In 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.

中文翻译：

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miR-130a-3p和SPOCK1在烟草暴露的支气管上皮BEAS-2B转化细胞中的作用：与A549和H1299肺癌细胞系的比较。

在由烟草烟雾引起的人肺癌的发病机理中，已知发生微RNA（miRNA）表达水平降低。目前，烟草烟雾和随后的肺细胞转化降低的特定miRNA表达水平仍有待确定。因此，本研究的目的是鉴定支气管上皮BEAS-2B细胞中的烟熏暴露后受到恶性转化为S30细胞的miRNA。另外，将S30转化的细胞中的miRNA与人肺癌细胞系A549和H1299进行了比较。我们的结果确定了在S30细胞以及A549和H1299肺癌细胞系中下调的miR-130a-3p。使用miRNA模拟，通过transwell和伤口愈合试验以及增强的细胞凋亡证明了miR-130a-3p表达水平升高与A549和H1299细胞系和S30细胞迁移减少之间的相关性。此外，使用两个在线靶基因预测程序TargetScan和miRDB来识别所有三种细胞类型中的miRNA靶基因SPOCK1。在未暴露的支气管上皮BEAS-2B细胞中，SPOCK1表达较高。令人感兴趣的是，注意到在暴露于香烟烟雾的转化的S30细胞中使SPOCK1沉默，导致细胞迁移明显降低。