Down-regulation of let-7 microRNA increased K-ras expression in lung damage induced by radon
Down-regulation of let-7 microRNA increased K-ras expression in lung damage induced by radon
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let-7 microRNA 的下调增加了氡诱导的肺损伤中 K-ras 的表达
DOI：
10.1016/j.etap.2015.08.009
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发表时间：
2015-09-01
影响因子：
4.3
通讯作者：
Nie, Jihua
中科院分区：
文献类型：
--
作者：
Chen, Zhihai;Wang, Dapeng;Nie, Jihua
氡长期以来被认为是导致肺癌的人类致癌物质，但其潜在机制仍不清楚。最近的研究表明，let-7 microRNA和K-ras在各种癌症的发展中起着重要作用。然而，let-7和K-ras在氡致肺损伤中的确切作用至今尚未被探讨。本研究采用Wistar大鼠和人支气管上皮细胞（HBE）长期暴露于氡，通过测定大鼠肺组织病理学改变、HBE细胞活性氧（ROS）、抗氧化酶活性和克隆形成以及let-7和K-ras表达的变化，观察氡对大鼠肺组织的毒性作用。结果表明，长期氡暴露可引起大鼠肺组织严重损伤，HBE细胞活性氧（ROS）生成量和克隆形成率显著增加，SOD活性显著降低。另外，氡暴露后，大鼠肺组织和HBE细胞let-7基因表达下调，K-ras基因表达上调。此外，然后证实在let-7 b-3 p和let-7a-2- 3 p转染的HBE细胞中K-ras的显著下调。以上结果提示let-7 microRNA和K-ras参与了体内和体外氡致肺损伤，对氡致肺肿瘤的早期诊断和治疗具有潜在价值。(C)2015爱思唯尔B. V.保留所有权利。
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. (C) 2015 Elsevier B.V. All rights reserved.