Аннотации:
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.