Effects of radon on miR-34a-induced apoptosis in human bronchial epithelial BEAS-2B cells
Effects of radon on miR-34a-induced apoptosis in human bronchial epithelial BEAS-2B cells
复制标题
氡对miR-34a诱导的人支气管上皮BEAS-2B细胞凋亡的影响
DOI：
10.1080/15287394.2019.1665350
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发表时间：
2019-09-09
影响因子：
2.6
通讯作者：
Li, Jianxiang
中科院分区：
文献类型：
--
作者：
Wu, Jing;Sun, Bin;Li, Jianxiang
摘要众所周知，氡暴露是肺癌发生的第二大诱因，其次是烟草暴露。在肺癌的发生发展过程中，microRNAs(MiRNAs)在调控与肺癌相关的各种靶基因方面发挥着重要作用。众所周知，细胞凋亡参与了消除癌细胞的过程。然而，慢性氡暴露诱导miRNAs调控的机制并不完全清楚，这些miRNAs调控被认为是导致癌变和随后激活细胞凋亡的结果。因此，这项研究的目的是研究慢性低水平氡暴露对肺miRNAs的作用，作为利用人支气管上皮BEAS-2B细胞进行致癌、诱导和随后激活细胞凋亡的模型。采用实时定量聚合酶链式反应(qRT-PCR)和流式细胞术检测miR-34a基因在BEAS-2B细胞中的表达和凋亡率。数据表明，慢性氡暴露可上调miR-34a的表达，并以时间依赖的方式促进细胞凋亡。Western印迹分析显示，miR-34a基因的过表达增加了细胞凋亡率，促进了Bax蛋白的表达，同时降低了抗凋亡基因Bcl2和PARP-1的蛋白表达。值得注意的是，转染了mi-R34a模拟物的BEAS-2B细胞的凋亡率增加，而转染mi-R34a抑制剂的细胞凋亡率降低。因此，证据表明，慢性氡暴露导致miR-34a基因上调，从而促进BEAS-2B细胞的凋亡。观察到的慢性氡暴露导致致癌的后果似乎涉及miR-34a基因的激活。
ABSTRACT 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.