The human long noncoding RNA lnc-IL7R regulates the inflammatory response.

The human long noncoding RNA lnc-IL7R regulates the inflammatory response.
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人类长链非编码 RNA lnc-IL7R 调节炎症反应。

DOI:
10.1002/eji.201344126
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发表时间:
2014-07
影响因子:
5.4
通讯作者:
Liu, Gang
Liu, Gang
中科院分区:
医学3区
文献类型:
--
作者:
Cui, Huachun;Xie, Na;Tan, Zheng;Banerjee, Sami;Thannickal, Victor John;Abraham, Edward;Liu, Gang

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长链非编码RNA(lncRNA),曾经被认为是转录噪音,最近被证明可以调节多种生物过程。然而,关于它们在炎症反应中的作用还没有太多的知识。在这项研究中,我们进行了人类lncRNA微阵列分析,并确定了一些lncRNA,表现出改变表达响应LPS刺激。在这些lncRNA中,与人白细胞介素-7受体α-亚基基因(IL-7 R)的3'非翻译区(3' UTR)重叠的lnc-IL-7 R在LPS处理的细胞中显著上调。在功能上,lnc-IL 7 R能够减少LPS诱导的炎症反应,这通过在lnc-IL 7 R敲低细胞中LPS诱导的E-选择素、VCAM-1、IL-6和IL-8的表达升高来证明。从机制上讲,我们发现lnc-IL 7 R敲低减少了组蛋白H3在赖氨酸27(H3 K27 me 3)处的三甲基化,这是沉默转录的标志,在炎症介质的近端启动子处。我们的数据表明,lnc-IL 7 R在炎症反应的调节中贡献了另一层复杂性。
Long noncoding RNAs (lncRNAs), once thought to be transcriptional noise, have been recently shown to regulate a variety of biological processes. However, there is not much knowledge regarding their roles in inflammatory response. In this study, we performed human lncRNA microarray assays and identified a number of lncRNAs that demonstrated altered expression in response to LPS stimulation. Of these lncRNAs, lnc-IL7R, which overlaps with the 3’ untranslated region (3’ UTR) of the human interleukin-7 receptor α-subunit gene (IL7R) gene, was significantly upregulated in LPS treated cells. Functionally, lnc-IL7R was capable of diminishing LPS-induced inflammatory response, demonstrated by elevated expression of LPS induced E-selectin, VCAM-1, IL-6 and IL-8 in lnc-IL7R knockdown cells. Mechanistically, we found that lnc-IL7R knockdown diminished trimethylation of histone H3 at lysine 27 (H3K27me3), a hallmark of silent transcription, at the proximal promoters of inflammatory mediators. Our data suggest that lnc-IL7R contributes another layer of complexity in regulation of inflammatory response.
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