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Published on: March 30, 2019
Down-regulation of let-7 microRNA increased K-ras expression in lung damage induced by radon
Zhihai Chen1, Dapeng Wang1, Chao Gu1
1Department of Toxicology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Medical College of Soochow University, Suzhou 215123, China.
Abstract:
Radon has long been recognized as a human carcinogen leading to lung cancer, but the underlying mechanisms remain obscure. Recent studies have shown that the let-7 microRNA and K-ras play an important role in the development of various cancers. However, the exact role between let-7 and K-ras in radon induced lung damage has not been explored so far. In the present study, wistar rats and human bronchial epithelial (HBE) cells were long-term exposed to radon, and then alterations in histological pathology of rat lung tissue, ROS, antioxidant enzymes activities and clonogenic formation in HBE cells, as well as changes in let-7 and K-ras expression were determined to observe the adverse effects induced by radon. The results showed that long-term exposure to radon produced severe lung damage in rats, significantly increased ROS production and clonogenic formation ratios and decreased SOD activities in HBE cells. In addition, an obvious down-regulation of let-7 and up-regulation of K-ras were also revealed both in mRNA and in protein level in lung tissue of rats and HBE cells exposed to radon. Furthermore, a significant down-regulation of K-ras was then confirmed in both let-7b-3p and let-7a-2-3p transfected HBE cells. Taken together, the present results propose an involvement of let-7 microRNA and K-ras in radon induced lung damage both in vivo and in vitro, which may thus be of potential value in early diagnosis and therapy of radon-induced lung tumorgenesis.
Insights
Radon exposure causes lung damage by altering let-7 microRNA and K-ras expression. This study reveals their role in radon-induced lung tumorigenesis, offering potential for early diagnosis and therapy.
Area of Science:
- Environmental Health
- Molecular Biology
- Oncology
Background:
- Radon is a known human carcinogen linked to lung cancer.
- The precise molecular mechanisms of radon-induced lung damage are not fully understood.
- let-7 microRNA and K-ras are implicated in various cancers, but their role in radon exposure is unexplored.
Purpose of the Study:
- To investigate the role of let-7 microRNA and K-ras in radon-induced lung damage.
- To examine histological, cellular, and molecular changes following long-term radon exposure in rats and human bronchial epithelial cells.
Main Methods:
- Wistar rats and human bronchial epithelial (HBE) cells were exposed to radon.
- Evaluated lung tissue histology, reactive oxygen species (ROS) production, antioxidant enzyme activity (SOD), and HBE cell clonogenic formation.
- Assessed let-7 microRNA and K-ras expression at both mRNA and protein levels.
- Investigated K-ras expression changes in HBE cells transfected with specific let-7 microRNAs.
Main Results:
- Radon exposure led to severe lung damage in rats.
- Increased ROS production and clonogenic formation, with decreased SOD activity in HBE cells.
- Observed down-regulation of let-7 and up-regulation of K-ras in lung tissue and HBE cells.
- Confirmed K-ras down-regulation in HBE cells with altered let-7 levels.
Conclusions:
- let-7 microRNA and K-ras are involved in radon-induced lung damage.
- Findings suggest a potential pathway for radon-induced lung tumorigenesis.
- These molecular alterations may serve as biomarkers for early diagnosis and therapeutic targets.
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