Department of General Biology and Genomics, Institute of Cell Biology and Biotechnology, L.N.Gumilyov Eurasian National University, Nur-Sultan, Akmola 010008, Kazakhstan.
Department of Experimental Medicine, University of Genoa, I-16132 Genoa, Italy.
Int J Mol Sci. 2020 Mar 20;21(6):2154. doi: 10.3390/ijms21062154.
Radon is the number one cause of lung cancer in non-smokers. microRNA expression in human bronchial epithelium cells is altered by radon, with particular reference to upregulation of miR-16, miR-15, miR-23, miR-19, miR-125, and downregulation of let-7, miR-194, miR-373, miR-124, miR-146, miR-369, and miR-652. These alterations alter cell cycle, oxidative stress, inflammation, oncogene suppression, and malignant transformation. Also DNA methylation is altered as a consequence of miR-29 modification induced by radon. Indeed miR-29 targets DNA methyltransferases causing inhibition of CpG sites methylation. Massive microRNA dysregulation occurs in the lung due to radon expose and is functionally related with the resulting lung damage. However, in humans this massive lung microRNA alterations only barely reflect onto blood microRNAs. Indeed, blood miR-19 was not found altered in radon-exposed subjects. Thus, microRNAs are massively dysregulated in experimental models of radon lung carcinogenesis. In humans these events are initially adaptive being aimed at inhibiting neoplastic transformation. Only in case of long-term exposure to radon, microRNA alterations lead towards cancer development. Accordingly, it is difficult in human to establish a microRNA signature reflecting radon exposure. Additional studies are required to understand the role of microRNAs in pathogenesis of radon-induced lung cancer.
氡是不吸烟人群肺癌的首要致病因素。氡会改变人类支气管上皮细胞中的 microRNA 表达，尤其会引起 miR-16、miR-15、miR-23、miR-19、miR-125 的上调和 let-7、miR-194、miR-373、miR-124、miR-146、miR-369 和 miR-652 的下调。这些改变会改变细胞周期、氧化应激、炎症、致癌基因抑制和恶性转化。此外，由于氡诱导的 miR-29 修饰，DNA 甲基化也发生改变。实际上，miR-29 靶向 DNA 甲基转移酶，导致 CpG 位点甲基化的抑制。由于氡暴露，肺部会发生大量 microRNA 失调，并且与导致的肺损伤具有功能相关性。然而，在人类中，这种大量的肺部 microRNA 改变几乎不会反映在血液 microRNAs 上。实际上，在氡暴露的受试者中并未发现血液 miR-19 发生改变。因此，在氡致肺癌发生的实验模型中 microRNAs 大量失调。在人类中，这些事件最初是适应性的，旨在抑制肿瘤转化。只有在长期暴露于氡的情况下，microRNA 的改变才会导致癌症的发展。因此，在人类中很难建立反映氡暴露的 microRNA 特征。需要进一步的研究来了解 microRNAs 在氡诱导肺癌发病机制中的作用。
