BioProject

miRNA Array was used to detect the expression level of miRNAs in human bronchial epithelial (HBE) cells that were transformed by a low-level arsenite exposure for 13 weeks. More...

miRNA Array was used to detect the expression level of miRNAs in human bronchial epithelial (HBE) cells that were transformed by a low-level arsenite exposure for 13 weeks. The transformed cells exhibited malignant phenotypes manifested by increased levels of cell proliferation, cell migration and high level of cell survival. Subsequently, 191 differentially expressed miRNAs are identified to be associated with arsenite-induced malignant transformation by employing miRNA Array. Among them, six miRNAs were chosen to validate their expression levels with qPCR and 17 miRNAs were further explored their target genes and the network. Three databases, TargetMiner, miRDB and TarBase, were used to predict the target genes of miRNAs and a total of 954 common genes were identified. Results of Gene Ontology (GO) analyses showed that these target genes were involved in diverse terms of GO categories, such as positive regulation of macroautophagy, epithelial cell maturation and synaptic vesicle clustering and so on. Moreover, results of KEGG pathway analyses demonstrated that most of these target genes were enriched in various cancer-related pathways including non-small cell lung cancer, Wnt signaling pathway, cell cycle, p53 signaling pathway and so forth. The miRNA-gene regulatory network, which was constructed by cytoscape software with miRNAs and their target genes, showed that the target genes were mainly regulated by miR-15b-5p, miR-106b-5p and miR-320d. Although more experimental verification is still needed to prove these predictions, our results may provide new insights into miRNA-mediated mechanisms underlying arsenite-induced malignant transformation. Overall design: in this study,191 differentially expressed miRNAs are associated with arsenite-induced malignant transformation by using microRNA Array. Among them, 17 miRNAs were chosen to further investigate their target genes and regulatory network. Our results provided the first evidence that most of these target genes of arsenite-related miRNAs were involved in diverse terms of GO categories enriched in various cancer-related pathways. Also, the miRNA-gene regulatory network was firstly constructed demonstrated that the modulation of the malignant transformation by miRNAs is complex. Our results indicate a dysregulation in the expression level of a panel of miRNAs which specific for arsenite-induced malignant transformation cells. The findings might help to promote the understanding of mechanisms underlying arsenite-induced carcinogenesis and provide some new and meaningful candidate miRNAs and genes to be further investigated after arsenite exposure. Less...