长链非编码RNA THRIL在脓毒症中上调，并通过吸附miR-19a在人支气管上皮细胞中上调肿瘤坏死因子-α。
LncRNA THRIL is upregulated in sepsis and sponges miR-19a to upregulate TNF-α in human bronchial epithelial cells.
作者信息
Liu Tao, Liu Jingbin, Tian Chunhua, Wang Hongyuan, Wen Min, Yan Mingyu
机构信息
Department of Respiratory and Critical Care Medicine, Inner Mongolia Baogang Hospital (The Third Affiliated Hospital of Inner Mongolia Medical University), Baotou, 014032 Inner Mongolia China.
Department of Respiratory Medicine, Hospital of FIRMACO (The Fourth Affiliated Hospital of Inner Mongolia Medical University), Baotou, 014032 Inner Mongolia China.
出版信息
J Inflamm (Lond). 2020 Sep 10;17:31. doi: 10.1186/s12950-020-00259-z. eCollection 2020.
BACKGROUND
Long non-coding RNAs (lncRNAs) have been demonstrated to play critical roles in various diseases. Our bioinformatics analysis showed that lncRNA TNFα and heterogenous nuclear ribonucleoprotein L (hnRNPL) related immunoregulatory LincRNA (THRIL) may interact with miR-19a, which targets TNF-α. This study aimed to explore the role of THRIL, an enhancer of LPS-induced inflammatory, in sepsis.
METHODS
Research subjects of the present study included 66 sepsis patients and 66 healthy volunteers. The expression levels of THRIL, miR-19a and TNF-α in plasma samples from these participants were determined by RT-qPCR. The interaction between THRIL and miR-19a was explored by performing overexpression experiments in human bronchial epithelial cells (HBEpCs). The roles of THRIL, miR-19a and TNF-α in regulating the apoptosis of HBEpCs were analyzed by cell apoptosis assay.
RESULTS
We found that THRIL was upregulated in sepsis patients. THRIL is predicted to interact with miR-19a, and the interaction was confirmed by dual-luciferase activity assay. However, THRIL and miR-19a did not affect the expression of each other. Instead, overexpression of THRIL resulted in the increased expression levels of TNF-α, a downstream target of miR-19a in HBEpCs. In HBEpCs, LPS treatment induced the overexpression of THRIL. Cell apoptosis analysis showed that overexpression of THRIL and TNF-α promoted the apoptosis of HBEpCs induced by LPS, while overexpression of miR-19a played an opposite role. Overexpression of THRIL attenuated the effects of overexpression of miR-19a.
CONCLUSION
Therefore, THRIL is upregulated in sepsis and may sponge miR-19a to upregulate TNF-α, thereby promoting lung cell apoptosis.
背景
长链非编码RNA（lncRNAs）已被证明在多种疾病中发挥关键作用。我们的生物信息学分析表明，lncRNA肿瘤坏死因子α与异质性核糖核蛋白L（hnRNPL）相关的免疫调节LincRNA（THRIL）可能与靶向肿瘤坏死因子-α（TNF-α）的miR-19a相互作用。本研究旨在探讨THRIL（一种脂多糖诱导炎症的增强子）在脓毒症中的作用。
方法
本研究的研究对象包括66例脓毒症患者和66名健康志愿者。通过逆转录定量聚合酶链反应（RT-qPCR）测定这些参与者血浆样本中THRIL、miR-19a和TNF-α的表达水平。通过在人支气管上皮细胞（HBEpCs）中进行过表达实验来探索THRIL与miR-19a之间的相互作用。通过细胞凋亡检测分析THRIL、miR-19a和TNF-α在调节HBEpCs凋亡中的作用。
结果
我们发现脓毒症患者中THRIL表达上调。预测THRIL与miR-19a相互作用，并且通过双荧光素酶活性测定证实了这种相互作用。然而，THRIL和miR-19a并不影响彼此的表达。相反，THRIL的过表达导致HBEpCs中miR-19a的下游靶标TNF-α表达水平升高。在HBEpCs中，脂多糖处理诱导THRIL过表达。细胞凋亡分析表明，THRIL和TNF-α的过表达促进了脂多糖诱导的HBEpCs凋亡，而miR-19a的过表达则起相反作用。THRIL的过表达减弱了miR-19a过表达的作用。
结论
因此，脓毒症中THRIL表达上调，可能通过吸附miR-19a上调TNF-α，从而促进肺细胞凋亡。
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