Cadmium (Cd) is an accumulative toxic metal which poses a serious threat to human health, even in trace amounts. One of the most important steps in the pathophysiology of lung cancer (LC) is the epithelial-mesenchymal transition (EMT). In this investigation, a cell malignant transformation model was established by exposing human bronchial epithelial cells (16HBE) to a low dose of Cd for 30 weeks, after which a highly expressed circular RNA (circ_000999) was identified. Cd-induced EMT was clearly observed in rat lungs and 16HBE cells, which was further enhanced following circ_000999-overexpression. Furthermore, upregulated EIF4A3 interacted with the parental gene AGTPBP1 to promote high expression of circ_000999. Subsequent experiments confirmed that circ_000999 could regulate the EMT process by competitively binding miR-205-5p and inhibiting its activity, consequently upregulating expression of zinc finger E-box binding protein 1 (ZEB1). Importantly, the circ_000999 expression level in LC tissues was significantly increased, exhibiting a strong correlation with EMT indicators. Overall, these findings provide a new objective and research direction for reversing lung EMT and subsequent treatment and prevention of LC.
Cadmium , Epithelial-Mesenchymal Transition , MicroRNAs , RNA, Circular , Zinc Finger E-box-Binding Homeobox 1 , Animals , Humans , Rats , Cadmium/toxicity , Cell Transformation, Neoplastic , Epithelial-Mesenchymal Transition/drug effects , Eukaryotic Initiation Factor-4A/genetics , Eukaryotic Initiation Factor-4A/metabolism , Lung Neoplasms/chemically induced , Lung Neoplasms/genetics , Lung Neoplasms/pathology , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Circular/genetics , RNA, Circular/metabolism , Zinc Finger E-box-Binding Homeobox 1/genetics , Zinc Finger E-box-Binding Homeobox 1/metabolism , Male
