School of Public Health, Medical College of Soochow University , Suzhou , JS , People's Republic of China.
School of Radiation Medicine and Protection, Medical College of Soochow University , Suzhou , JS , People's Republic of China.
J Toxicol Environ Health A. 2019;82(16):913-919. doi: 10.1080/15287394.2019.1665350. Epub 2019 Sep 8.
Radon exposure is known to be the second most frequent cause followed by tobacco exposure for lung cancer development. In lung cancer development, microRNAs (miRNAs) play an important role in regulating various target genes associated with this disease. It is well-established that apoptosis is involved in the elimination of cancer cells. However, the mechanisms underlying chronic radon exposure induced miRNAs regulation attributed to result in carcinogenesis and subsequent activation of apoptosis is not completely understood. The aim of this study was thus to examine chronic low level radon exposure on lung miRNAs as a model for carcinogenesis induction and subsequent activation of apoptosis using human bronchial epithelial BEAS-2B cells. Quantitative real-time PCR (qRT-PCR) and flow cytometry were used to determine the miR-34a gene expression and apoptotic rate in BEAS-2B cells. Data demonstrated that chronic radon exposure up-regulated the expressions of miR-34a and enhanced cellular apoptosis in a time-dependent manner. Western blot analysis demonstrated that overexpression of the gene miR-34a enhanced apoptotic rate and elevated proapoptotic Bax protein expression accompanied by decreased protein expressions of antiapoptotic Bcl-2 and PARP-1. It is noteworthy that the apoptotic rate was elevated in BEAS-2B cells transfected with mi-R34a mimic but reduced in mi-R34a inhibitor-transfected cells. Evidence thus indicates that chronic exposure to radon produced up-regulation of miR-34a gene which subsequently enhanced apoptosis in BEAS-2B cells. The observed consequences following chronic radon exposure leading to carcinogenesis appear to involve activation of miR-34a gene.
氡暴露已知是仅次于烟草暴露的肺癌发展的第二大常见原因。在肺癌发展中，microRNAs（miRNAs）在调节与该疾病相关的各种靶基因方面发挥着重要作用。凋亡参与癌细胞的消除已得到充分证实。然而，慢性氡暴露诱导 miRNAs 调节导致致癌作用以及随后凋亡的激活的机制尚不完全清楚。因此，本研究旨在使用人支气管上皮 BEAS-2B 细胞作为致癌作用诱导和随后凋亡激活的模型，研究慢性低水平氡暴露对肺 miRNAs 的影响。定量实时 PCR（qRT-PCR）和流式细胞术用于确定 BEAS-2B 细胞中 miR-34a 基因的表达和凋亡率。数据表明，慢性氡暴露以时间依赖性方式上调 miR-34a 的表达并增强细胞凋亡。Western blot 分析表明，miR-34a 基因的过表达增强了凋亡率，并升高了促凋亡 Bax 蛋白的表达，同时降低了抗凋亡 Bcl-2 和 PARP-1 的蛋白表达。值得注意的是，miR-34a 模拟物转染的 BEAS-2B 细胞中的凋亡率升高，而 miR-34a 抑制剂转染的细胞中的凋亡率降低。因此，有证据表明，慢性氡暴露会导致 miR-34a 基因的上调，进而增强 BEAS-2B 细胞中的凋亡。观察到的慢性氡暴露导致致癌作用的后果似乎涉及 miR-34a 基因的激活。
