LncRNA-MEG3 functions as a competing endogenous RNA to regulate Treg/Th17 balance in patients with asthma by targeting microRNA-17/ RORγt
LncRNA-MEG3 functions as a competing endogenous RNA to regulate Treg/Th17 balance in patients with asthma by targeting microRNA-17/ RORγt
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DOI：
10.1016/j.biopha.2018.12.080
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发表时间：
2019-03-01
影响因子：
7.5
通讯作者：
Qin, Chu
中科院分区：
文献类型：
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作者：
Qiu, Yu-ying;Wu, Yan;Qin, Chu
背景：Treg/Th17失衡在哮喘的发病机制中起着重要作用。哮喘中观察到了紊乱的LncRNA，但LncRNA是否能够调节Treg/Th17平衡及其机制仍有待研究。方法：采用微阵列技术鉴定哮喘患者和健康对照者外周血CD4+T细胞中差异表达的lncRNA和microRNA。利用生物信息证据来选择可能参与调节Treg/Th17平衡的候选lncRNA和microRNA。在体外实验中确定了 LncRNA-MEG3 和 microRNA-17 对 CD4 + T 细胞群改变的功能。同时，估计了LncRNA-MEG3和microRNA-17对ROR gamma t或Foxp3的调节作用。通过双荧光素酶报告基因测定和RNA pull-down证实了LncRNA-MEG3与microRNA-17的相互作用。结果：选择25个lncRNA和19个microRNA作为候选基因，这些基因在哮喘患者的CD4 + T细胞中与健康对照者差异表达，并且有可能通过调节ROR gamma t或Foxp3来控制Treg/Th17平衡。 LncRNA-MEG3 的交替改变了功能并增加了 Th17 的百分比。 LncRNA-MEG3可以调节ROR gamma t mRNA和蛋白水平。 LncRNA-MEG3 可以作为竞争性内源 RNA (ceRNA) 抑制 microRNA-17 的水平。 microRNA-17通过直接靶向ROR gamma t来抑制Th17。结论：LncRNA-MEG3可以将microRNA-17作为ceRNA海绵，从而调节ROR gamma t，最终影响哮喘中的Treg/Th17平衡。 lncRNA/microRNA轴可能在疾病的临床治疗和诊断中具有潜在的应用。
Background: Treg/Th17 imbalance plays an essential role in the pathogenesis of asthma. Disordered LncRNAs were observed in asthma, however, whether LncRNAs can regulate the Treg/Th17 balance and its mechanism still needs to be investigated.Methods: Microarrays were performed to identify the differentially expressed lncRNAs and microRNAs in peripheral blood CD4 + T cells from patients with asthma and healthy controls. Bioinformatical evidence was used to select candidate lncRNAs and microRNAs which may involve in regulation of Treg/Th17 balance. The function of LncRNA-MEG3 and microRNA-17 on the alteration of the CD4 + T cell population were determined in vitro experiments. Meanwhile, the regulatory effect of LncRNA-MEG3 and microRNA-17 on ROR gamma t or Foxp3 was estimated. The interaction of LncRNA-MEG3 with microRNA-17 was confirmed by dual luciferase reporter assay and RNA pull-down.Results: 25 lncRNAs and 19 microRNAs were selected as candidate genes which differentially expressed in CD4 + T cells from patients with asthma compared with healthy controls and had potential to control Treg/Th17 balance by regulating ROR gamma t or Foxp3. Alternation of LncRNA-MEG3 changed the function and increased the percentage of Th17. LncRNA-MEG3 could regulate the ROR gamma t mRNA and protein level. LncRNA-MEG3 could inhibit the level of microRNA-17 as a competing endogenous RNA (ceRNA). microRNA-17 suppressed Th17 though targeting ROR gamma t directly.Conclusion: LncRNA-MEG3 can sponge microRNA-17 as a ceRNA, thereby regulating ROR gamma t and ultimately affecting Treg/Th17 balance in asthma. The lncRNA/microRNA axis may have potential application in clinical treatment and diagnosis of the disease.