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lncRNAs在低剂量电离辐射暴露小鼠外周血单个核细胞免疫反应中作用的综合分析

Integrative Analysis for the Roles of lncRNAs in the Immune Responses of Mouse PBMC Exposed to Low-Dose Ionizing Radiation.

作者信息

Qi Zhenhua, Guo Sitong, Li Changyong, Wang Qi, Li Yaqiong, Wang Zhidong

机构信息

Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China.

出版信息

Dose Response. 2020 Mar 24;18(1):1559325820913800. doi: 10.1177/1559325820913800. eCollection 2020 Jan-Mar.

Abstract

It is well accepted that low-dose ionizing radiation (LDIR) modulates a variety of immune responses that have exhibited the properties of immune hormesis. Alterations in messenger RNA (mRNA) and long noncoding RNA (lncRNA) expression were to crucially underlie these LDIR responses. However, lncRNAs in LDIR-induced immune responses have been rarely reported, and its functions and molecular mechanisms have not yet been characterized. Here, we used microarray profiling to determine lncRNA in BALB/c mice exposed to single (0.5 Gy×1) and chronic (0.05 Gy×10) low-dose γ-rays radiation (Co). We observed that a total of 8274 lncRNAs and 7240 mRNAs were altered in single LDIR, while 2077 lncRNAs and 796 mRNAs in chronic LDIR. The biological functions of these upregulated mRNAs in both 2 groups using Gene Ontology functional and pathway enrichment analysis were significantly enriched in immune processes and immune signaling pathways. Subsequently, we screened out the lncRNAs involved in regulating these immune signaling pathways and examined their potential functions by lncRNAs-mRNAs coexpression networks. This is the first study to comprehensively identify lncRNAs in single and chronic LDIR responses and to demonstrate the involvement of different lncRNA expression patterns in LDIR-induced immune signaling pathways. Further systematic research on these lncRNAs will provide new insights into our understanding of LDIR-modulated immune hormesis responses.

摘要

低剂量电离辐射(LDIR)可调节多种免疫反应,这些反应已表现出免疫兴奋效应的特性,这一点已得到广泛认可。信使核糖核酸(mRNA)和长链非编码核糖核酸(lncRNA)表达的改变是这些LDIR反应的关键基础。然而,关于LDIR诱导的免疫反应中的lncRNAs报道很少,其功能和分子机制尚未得到表征。在此,我们使用微阵列分析来确定暴露于单次(0.5 Gy×1)和慢性(0.05 Gy×10)低剂量γ射线辐射(钴)的BALB/c小鼠中的lncRNA。我们观察到,单次LDIR中有总共8274个lncRNAs和7240个mRNAs发生改变,而慢性LDIR中有2077个lncRNAs和796个mRNAs发生改变。使用基因本体功能和通路富集分析,这两组中这些上调的mRNAs的生物学功能在免疫过程和免疫信号通路中显著富集。随后,我们筛选出参与调节这些免疫信号通路的lncRNAs,并通过lncRNAs-mRNAs共表达网络研究它们的潜在功能。这是第一项全面鉴定单次和慢性LDIR反应中lncRNAs,并证明不同lncRNA表达模式参与LDIR诱导的免疫信号通路的研究。对这些lncRNAs进行进一步的系统研究将为我们理解LDIR调节的免疫兴奋效应反应提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7cf/7093697/ac55eace377a/10.1177_1559325820913800-fig1.jpg

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