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.

中文翻译：

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EIF4A3调节的circ_000999通过miR-205-5p/ZEB1轴促进镉诱导的恶性转化中的上皮-间质转化

镉 (Cd) 是一种累积性有毒金属，即使微量，也会对人类健康构成严重威胁。肺癌（LC）病理生理学中最重要的步骤之一是上皮-间质转化（EMT）。在这项研究中，通过将人支气管上皮细胞（16HBE）暴露于低剂量的Cd 30周，建立了细胞恶性转化模型，之后鉴定出高表达的环状RNA（circ_000999）。在大鼠肺和 16HBE 细胞中清楚地观察到 Cd 诱导的 EMT，并且在 circ_000999 过表达后进一步增强。此外，上调的 EIF4A3 与亲本基因 AGTPBP1 相互作用，促进 circ_000999 的高表达。随后的实验证实，circ_000999可以通过竞争性结合miR-205-5p并抑制其活性来调节EMT过程，从而上调锌指E-box结合蛋白1（ZEB1）的表达。重要的是，LC组织中circ_000999的表达水平显着升高，与EMT指标呈强相关性。总体而言，这些发现为逆转肺EMT以及后续LC的治疗和预防提供了新的目标和研究方向。