LncRNA RP11-86H7.1 promotes airway inflammation induced by TRAPM2.5 by acting as a ceRNA of miRNA-9-5p to regulate NFKB1 in HBECS
LncRNA RP11-86H7.1 promotes airway inflammation induced by TRAPM2.5 by acting as a ceRNA of miRNA-9-5p to regulate NFKB1 in HBECS
复制标题
LncRNA RP11-86H7.1通过作为miRNA-9-5p的ceRNA调节HBECS中的NFKB1促进TRAPM2.5诱导的气道炎症
DOI：
10.1038/s41598-020-68327-1
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发表时间：
2020
影响因子：
4.6
通讯作者：
Ran Pixin
中科院分区：
文献类型：
--
作者：
Zhao Jun;Pu Jinding;Hao Binwei;Huang Lingmei;Chen Jinglong;Hong Wei;Zhou Yumin;Li Bing;Ran Pixin
交通相关空气污染颗粒物2.5(TRAPM2.5)与以呼吸道炎症为特征的慢性阻塞性肺疾病(COPD)有关。具体地说，这些有害颗粒或气体会增加慢性呼吸道炎症。最近的一些研究表明，lncRNAs与COPD密切相关，并参与了呼吸道炎症的调节。然而，确切的机制仍不清楚。在本研究中，我们研究了TRAPM2.5对人支气管上皮细胞(HBECs)气道炎症的影响及其由lncRNA介导的潜在机制。TRAPM2.5作用于HBECs后，新的lncRNA RP11-86H7.1显著上调。功能分析表明，TRAPM2.5诱导HBECs表达炎症因子需要lncRNA RP11-86H7.1。一项机制研究表明，LncRNARP11-86H7.1可能通过激活NF-κB信号通路参与TRAPM2.5诱导的炎症反应。此外，lncRNARP11-86H7.1作为miR-9-5p的内源性竞争核糖核酸，逆转其靶基因NFKB1的抑制作用，维持NF-κB的激活，从而促进炎症反应。综上所述，我们的研究阐明了lncRNA RP11-86H7.1-miR-9-5p-NFKB1调节网络在TRAPM2.5诱导的气道炎症中的促炎作用，并表明该网络的组成部分可能作为新的诊断生物标志物和潜在的治疗靶点。
Traffic-related air pollution particulate matter 2.5 (TRAPM2.5), is involved in chronic obstructive pulmonary disease (COPD), which is characterized by airway inflammation. Specifically, these harmful particles or gases can increase chronic airway inflammation. Some recent studies have shown that lncRNAs are closely related to COPD and participate in the regulation of airway inflammation. However, the precise mechanisms remain unknown. In the present study, we investigated the effect of TRAPM2.5 on airway inflammation in human bronchial epithelial cells (HBECs) and the underlying mechanisms mediated by a lncRNA. After exposure to TRAPM2.5, the novel lncRNA RP11-86H7.1 was markedly upregulated in HBECs. Functional assays indicated that the lncRNA RP11-86H7.1 was required for the TRAPM2.5-induced expression of inflammatory factors in HBECs. A mechanistic study demonstrated that lncRNA RP11-86H7.1 might participate in TRAPM2.5-induced inflammatory responses by activating the NF-κB signaling pathway. Moreover, the lncRNA RP11-86H7.1 can promote the inflammatory response by acting as a competing endogenous RNA of miR-9-5p, reversing the inhibitory effect of its target gene NFKB1, and sustaining NF-κB activation. In summary, our study elucidates the pro-inflammatory roles of the lncRNA RP11-86H7.1–miR-9-5p–NFKB1 regulatory network in airway inflammation induced by TRAPM2.5 and indicates that the components of this network might serve as novel diagnostic biomarkers and potential therapeutic targets.