Chen Zhihai, Wang Dapeng, Gu Chao, Liu Xing, Pei Weiwei, Li Jianxiang, Cao Yi, Jiao Yang, Tong Jian, Nie Jihua
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.
School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.
Environ Toxicol Pharmacol. 2015 Sep;40(2):541-8. doi: 10.1016/j.etap.2015.08.009. Epub 2015 Aug 12.
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.
长期以来，氡一直被认为是导致肺癌的人类致癌物，但其潜在机制仍不清楚。最近的研究表明，let-7微小RNA和K-ras在各种癌症的发展中起重要作用。然而，let-7和K-ras在氡诱导的肺损伤中的确切作用迄今尚未得到探讨。在本研究中，将Wistar大鼠和人支气管上皮（HBE）细胞长期暴露于氡，然后测定大鼠肺组织的组织病理学变化、活性氧（ROS）、抗氧化酶活性以及HBE细胞中的克隆形成，以及let-7和K-ras表达的变化，以观察氡诱导的不良反应。结果表明，长期暴露于氡会使大鼠产生严重的肺损伤，显著增加ROS的产生和克隆形成率，并降低HBE细胞中的超氧化物歧化酶（SOD）活性。此外，在暴露于氡的大鼠肺组织和HBE细胞中，let-7在mRNA和蛋白质水平均明显下调，K-ras则上调。此外，在转染了let-7b-3p和let-7a-2-3p的HBE细胞中均证实K-ras显著下调。综上所述，本研究结果表明let-7微小RNA和K-ras在体内和体外的氡诱导的肺损伤中均有参与，这可能在氡诱导的肺肿瘤发生的早期诊断和治疗中具有潜在价值。
