Down-regulation of let-7 microRNA increased K-ras expression in lung damage induced by radon

Chen, Zhihai; Wang, Dapeng; Gu, Chao; Liu, Xing; Pei, Weiwei; Li, Jianxiang; Cao, Yi; Jiao, Yang; Tong, Jian; Nie, Jing

doi:10.1016/j.etap.2015.08.009

Cited by 26 publications

(19 citation statements)

References 39 publications

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“…Chen et al reported that the level of expression of let-7 microRNA in human bronchial epithelial (HBE) cells due to radon exposure is decreasing, which results in activation of the K-ras oncogene. Furthermore, a significant down-regulation of K-ras was then confirmed in both let-7b-3p and let-7a-2-3p transfected HBE cells [103]. The results of this study proposed that let-7 microRNA and K-ras are involved in radon-induced lung damage both in vivo and in vitro.…”

Section: Ma Et Al Demonstrated That Overexpression Of Mir-622 In Colsupporting

confidence: 54%

Residential Radon Exposure and Lung Cancer Risk in Kazakhstan

Bersimbaev¹,

Bulgakova²

2017

Radon

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Many published data have demonstrated the potential of radon exposure to induce biological damage. All these studies suggest that exposure to radon and its progeny can represent a significant public health risk. Radon exposure is considered as the second cause of lung cancer and it is the first in never smokers. Many countries have depicted residential radon exposure maps in order to characterize those areas with the highest indoor radon concentrations. There are areas in Kazakhstan with a number of factors leading to natural radioactivity. The genotoxic effects of radon on population of Kazakhstan are poorly understood. These studies conducted in compliance with all requirements of genotoxic studies will provide an extensive and reliable data for a detailed radon zoning of Kazakhstan. Our review attempts to integrate data about the association between residential radon levels and morbidity of population in Kazakhstan. In addition, we tried to cover all points of the cytogenetic and molecular changes induced by radon exposure.

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Section: Ma Et Al Demonstrated That Overexpression Of Mir-622 In Colsupporting

confidence: 54%

Residential Radon Exposure and Lung Cancer Risk in Kazakhstan

Bersimbaev¹,

Bulgakova²

2017

Radon

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“…Food and water were available ad libitum during the exposure. Control mice were housed in a same room with a background concentration of radon at 20 Bq/m 3 [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

Circular RNA profiles in mouse lung tissue induced by radon

Pei

Tao

Zhang

et al. 2017

Environ Health Prev Med

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BackgroundRadon is a known human lung carcinogen, whose underlying carcinogenic mechanism remains unclear. Recently, circular RNA (circRNA), a class of endogenous non-protein coding RNAs that contain a circular loop, was found to exhibit multiple biological effects. In this study, circRNA profiles in mouse lung tissues between control and radon exposure were analyzed.MethodsSix mice were exposed to radon at concentration of 100,000 Bq/m3, 12 h/d, for up to cumulative doses of 60 working level months (WLM). H&E staining and immunohistochemistry of caspase-3 were used to detect the damages in lung tissue. The lung tissue of control and exposed group were selected for circRNA microarray study. The circRNA/microRNA interaction was analyzed by starBase prediction software. 5 highest expressing circRNAs were selected by real-time PCR to validate the consistency in mouse lung tissue exposed to radon.ResultsInflammatory reaction was found in mouse lung tissue exposed to radon, and caspase-3 expression was significantly increased. Microarray screening revealed 107 up-regulated and 83 down-regulated circRNAs, among which top 30 circRNAs with the highest fold changes were chosen for further analysis, with 5 microRNAs binding sites listed for each circRNA. Consistency of the top 5 circRNAs with the highest expressions were confirmed in mice exposed with 60WLM of radon.ConclusionMouse lung tissue was severely injured when exposed to radon through pathological diagnosis and immunohistochemical analysis. A series of differentially expressed circRNAs demonstrated that they may play an important role in pulmonary toxicity induced by radon.

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“…Emerging data show that inhibition of tumor growth may occur via suppression of K-ras expression by miRNA let-7a. let-7 and K-ras alteration have been reported to occur in rat lung tissues and human bronchial epithelial cells upon exposure to radon [93].…”

Section: Epigenetic Factors In the Development Of Radon-induced Lung mentioning

confidence: 99%

“…Chronic exposure to radon induces oxidative damage, let-7 downregulation and consequent mutant K-ras over-expression both in human bronchial epithelial cells [93]. Ionizing radiation that affects cells changes the pattern of DNA methylation [89].…”

Section: Epigenetic Factors In the Development Of Radon-induced Lung mentioning

confidence: 99%

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Radon Biomonitoring and microRNA in Lung Cancer

Bersimbaev

Pulliero

Bulgakova

et al. 2020

IJMS

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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.

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Down-regulation of let-7 microRNA increased K-ras expression in lung damage induced by radon

Cited by 26 publications

References 39 publications

Residential Radon Exposure and Lung Cancer Risk in Kazakhstan

Residential Radon Exposure and Lung Cancer Risk in Kazakhstan

Circular RNA profiles in mouse lung tissue induced by radon

Radon Biomonitoring and microRNA in Lung Cancer

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