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.
MicroRNAs are a class of small noncoding endogenous RNAs 19–25 nucleotides long, which play an important role in the post-transcriptional regulation of gene expression by targeting mRNA targets with subsequent repression of translation. MicroRNAs are involved in the pathogenesis of numerous diseases, including cancer. Lung cancer is the leading cause of cancer death in the world. Lung cancer is usually associated with tobacco smoking. However, about 25% of lung cancer cases occur in people who have never smoked. According to the International Agency for Research on Cancer, asbestos has been classified as one of the cancerogenic factors for lung cancer. The mechanism of malignant transformation under the influence of asbestos is associated with the genotoxic effect of reactive oxygen species, which initiate the processes of DNA damage in the cell. However, epigenetic mechanisms such as changes in the microRNA expression profile may also be implicated in the pathogenesis of asbestos-induced lung cancer. Numerous studies have shown that microRNAs can serve as a biomarker of the effects of various adverse environmental factors on the human body. This review examines the role of microRNAs, the expression profile of which changes upon exposure to asbestos, in key processes of carcinogenesis, such as proliferation, cell survival, metastasis, neo-angiogenesis, and immune response avoidance.
Radon is one of the most powerful carcinogens, particularly in terms of lung cancer onset and development. miRNAs may be considered not only as markers of the ongoing tumorigenesis but also as a hallmark of exposure to radiation, including radon and its progeny. Therefore, the purpose of the present study was to estimate the value of plasma miR-19b-3p level as the prospective marker of the response to radon exposure in lung cancer pathogenesis. A total of 136 subjects were examined, including 49 radon-exposed patients with lung cancer, 37 patients with lung cancer without radon exposure and 50 age/sex matched healthy controls. Total RNA from blood samples was extracted and used to detect miR-19b-3p expression via reverse transcription quantitative-polymerase chain reaction. The 2 method was used to quantify the amount of relative miRNA. The plasma level of p53 protein was determined using a Human p53 ELISA kit. Plasma miR-19b-3p level was significantly higher in the patients with lung cancer groups, compared with the healthy control group (P<0.0001). No other statistically significant differences were determined in the expression level of plasma miR-19b-3p between patients diagnosed with lung cancer exposed to radon and not exposed to radon. The expression level of free circulating miR-19b-3p was higher in the group of non-smoking patients with lung cancer, compared with smokers with lung cancer. The miR-19b-3p was 1.4-fold higher in non-smokers than in smokers (P<0.05). No association between plasma levels of p53 protein and miR-19b-3p freely circulating in patients with lung cancer was observed. No other statistically significant differences were determined in the plasma p53 protein level between patients diagnosed with lung cancer exposed and not exposed to radon. These results indicated that detection of miR-19b-3p levels in plasma potentially could be exploited as a noninvasive method for the lung cancer diagnostics. However, this miRNA is not suitable as the precise marker for radon impact.
MicroRNAs are short, non-coding RNA molecules regulating gene expression by inhibiting the translation of messenger RNA (mRNA) or leading to degradation. The miRNAs are encoded in the nuclear genome and exported to the cytosol. However, miRNAs have been found in mitochondria and are probably derived from mitochondrial DNA. These miRNAs are able to directly regulate mitochondrial genes and mitochondrial activity. Mitochondrial dysfunction is the cause of many diseases, including cancer. In this review, we consider the role of mitochondrial miRNAs in the pathogenesis of lung cancer with particular reference to radon exposure.
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