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氡暴露小鼠肺组织中长链非编码 RNA 的表达谱。

Expression profiles of long non-coding RNA in mouse lung tissue exposed to radon.

机构信息

School of Public Health, Medical College of Soochow University , Suzhou , China.

Jiangsu Key Laboratory of Preventive and Translational Medicine for Genetic Diseases , Suzhou , China.

出版信息

J Toxicol Environ Health A. 2019;82(15):854-861. doi: 10.1080/15287394.2019.1664011. Epub 2019 Sep 8.

Abstract

Long non-coding RNAs (lncRNA) exert biological functions by interacting with RNAs, proteins, and DNA. Although lung damage associated with radon exposure was attributed to disturbances in microRNA and protein expression, the influence of radon on lncRNA is at present not known. The aim of this study was to (1) examine the effect of radon on lncRNA-mediated expression of transcription factors in mRNA in mouse lung tissue and (2) determine potential function and targets. Female BALB/c mice were divided into two groups: control and radon exposure to approximately 100,000 Bq/m (equivalent up to 60 working level month, WLM).RNA was extracted from lung tissue and used for high through-put lncRNA microarray analysis. A total of 1256 lncRNA transcripts were differentially expressed between the two groups of mice. Among these, the top 200 lncRNA-mRNA sets, with fold change of >2 and , were selected for KEGG analysis. Functional analysis via bioinformatics prediction in this study also suggested involvement of ErbB and Notch pathways in radon-induced mouse pulmonary injury. The results from immunohistochemical and Western blot analysis indicated that EbB2 and k-Ras protein expressions were significantly increased. In conclusion, approximately 1,000 dysregulated lncRNA transcripts were found in radon-exposed mice and these lncRNA may play an important role in lung damage following radon exposure. The observations in this study also suggested that ErbB2 and Notch pathways are activated and may be involved in radon-induced pulmonary toxicity.

摘要

长链非编码 RNA(lncRNA)通过与 RNA、蛋白质和 DNA 相互作用发挥生物学功能。虽然与氡暴露相关的肺损伤归因于 microRNA 和蛋白质表达的紊乱,但目前尚不清楚氡对 lncRNA 的影响。本研究的目的是:(1) 检测氡对小鼠肺组织中 lncRNA 介导的转录因子 mRNA 表达的影响;(2) 确定潜在的功能和靶标。将雌性 BALB/c 小鼠分为两组:对照组和氡暴露组,氡暴露量约为 100,000 Bq/m(相当于 60 个工作水平月,WLM)。从肺组织中提取 RNA,并用于高通量 lncRNA 微阵列分析。两组小鼠之间共有 1256 个 lncRNA 转录本表达差异。在这些差异表达的 lncRNA 中,选择倍数变化>2 和 的前 200 个 lncRNA-mRNA 进行 KEGG 分析。本研究通过生物信息学预测进行的功能分析还表明,ErbB 和 Notch 通路参与了氡诱导的小鼠肺损伤。免疫组织化学和 Western blot 分析的结果表明,EbB2 和 k-Ras 蛋白表达明显增加。总之,在氡暴露的小鼠中发现了大约 1000 个失调的 lncRNA 转录本,这些 lncRNA 可能在氡暴露后肺损伤中发挥重要作用。本研究的观察结果还表明,ErbB2 和 Notch 通路被激活,可能参与了氡诱导的肺毒性。

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