Long‐term arsenic exposure can promote cancer through epigenetic mechanisms, and arsenite methyltransferase (AS3MT) plays an important role in this process. However, the expression patterns and mechanisms of AS3MT in arsenic carcinogenesis remain unclear. In this study, we found that the AS3MT was overexpressed in arsenic exposed population, non‐small cell lung cancer (NSCLC) tissues, and A549 cells with sodium arsenite (NaAsO2) treatment for 48 hours. Besides, the level of AS3MT expression was positively correlated with the concentrations of urinary total arsenic (tAs), inorganic arsenic (iAs), methanearsonic acid (MMA), and dimethylarsinic acid (DMA) in all subjects. Functional experiments demonstrated that siRNA‐mediated knockdown of AS3MT significantly inhibited proliferation of A549 cells. Mechanism investigation revealed that silencing of AS3MT inhibited proliferation by increasing mRNA expression levels of p21 and E2F1, and inhibiting CDK1, CDK2, CDK4, CDK6, Cyclin A2, Cyclin E1, Cyclin E2, and PCNA mRNA expression. Therefore, arsenic increased AS3MT expression in vivo and in vitro, which could directly act on the cell and affect the progression of NSCLC by regulating cell cycle genes.

中文翻译：

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无机砷介导的AS3MT上调通过调节细胞周期基因促进非小细胞肺癌细胞增殖

长期接触砷可通过表观遗传机制促进癌症发生，而亚砷酸甲基转移酶（AS3MT）在这一过程中起着重要作用。然而，AS3MT 在砷致癌作用中的表达模式和机制仍不清楚。在本研究中，我们发现 AS3MT 在砷暴露人群、非小细胞肺癌 (NSCLC) 组织和亚砷酸钠 (NaAsO2) 处理 48 小时的 A549 细胞中过度表达。此外，AS3MT的表达水平与所有受试者的尿总砷（tAs）、无机砷（iAs）、甲胂酸（MMA）和二甲基胂酸（DMA）的浓度呈正相关。功能实验表明，siRNA 介导的 AS3MT 敲低显着抑制了 A549 细胞的增殖。机制研究表明，沉默 AS3MT 通过增加 p21 和 E2F1 的 mRNA 表达水平，并抑制 CDK1、CDK2、CDK4、CDK6、Cyclin A2、Cyclin E1、Cyclin E2 和 PCNA mRNA 表达来抑制增殖。因此，砷在体内外均增加AS3MT表达，可直接作用于细胞，通过调节细胞周期基因影响NSCLC的进展。