title: Down-regulation of let-7 microRNA increased K-ras expression in lung damage induced by radon.
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.
authors: Department 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.
authors: Zhihai
authors: Z
authors: Chen
authors: Department 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.
authors: Dapeng
authors: D
authors: Wang
authors: Department 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.
authors: Chao
authors: C
authors: Gu
authors: Department 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.
authors: Xing
authors: X
authors: Liu
authors: Department 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.
authors: Weiwei
authors: W
authors: Pei
authors: Department 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.
authors: Jianxiang
authors: J
authors: Li
authors: Department 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.
authors: Yi
authors: Y
authors: Cao
authors: School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.
authors: Yang
authors: Y
authors: Jiao
authors: Department 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. Electronic address: tongjian@suda.edu.cn.
authors: Jian
authors: J
authors: Tong
authors: Department 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. Electronic address: niejihua@suda.edu.cn.
authors: Jihua
authors: J
authors: Nie
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000378:metabolism; D011886:Radon / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C117307:KRAS protein, human; C528430:Kras protein, rat; C548145:MIRNLET7 microRNA, rat; D035683:MicroRNAs; D017382:Reactive Oxygen Species; C487931:mirnlet7 microRNA, human; D016283:Proto-Oncogene Proteins p21(ras); D011886:Radon
keywords: K-ras; Let-7; MicroRNA; Radon