Li Lihua, Zhang Shaorong, Jiang Xunshuo, Liu Yuehui, Liu Ke, Yang Chunping
Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Exp Ther Med. 2018 Apr;15(4):3523-3529. doi: 10.3892/etm.2018.5827. Epub 2018 Feb 1.
The present study aimed to explore the microRNA-let-7e (miR-let-7e) expression in allergic rhinitis (AR), and to investigate the underlying molecular mechanisms. miR-let-7e expression in the nasal mucosa of mice and patients with AR were detected. The expression levels of three inflammatory factors, including histamine, immunoglobulin E and tumor necrosis factor-α (TNF-α), in the blood of AR mice and in interleukin (IL)-13-stimulated nasal epithelial cells (NECs) were also measured. Furthermore, the target gene of miR-let-7e was predicted and validated using a luciferase reporter assay. The expression levels of Janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3) were detected. The results demonstrated that miR-let-7e was downregulated in patients and mice with AR compared with the controls. In addition, the expression levels of inflammatory factors were higher in the blood of mice with AR compared with the control group, while miR-let-7e overexpression inhibited these levels in AR mice and IL-13-stimulated NECs. Furthermore, suppressor of cytokine signaling 4 (SOCS4) was revealed as a potential target gene of miR-let-7e and was negatively regulated by miR-let-7e. Overexpression of SOCS4 abrogated the anti-inflammatory activity of miR-let-7e overexpression. Finally, miR-let-7e overexpression activated the JAK1/STAT3 signaling pathway. In conclusion, miR-let-7e may serve an important role in the progression and development of AR, while overexpression of miR-let-7e had an anti-inflammatory effect by targeting SOCS4, which may be achieved by activation of the JAK1/STAT3 signaling pathway.
本研究旨在探讨微小RNA-let-7e（miR-let-7e）在变应性鼻炎（AR）中的表达情况，并研究其潜在的分子机制。检测了AR小鼠和患者鼻黏膜中miR-let-7e的表达。还测定了AR小鼠血液以及白细胞介素（IL）-13刺激的鼻上皮细胞（NECs）中三种炎症因子（组胺、免疫球蛋白E和肿瘤坏死因子-α（TNF-α））的表达水平。此外，使用荧光素酶报告基因检测法预测并验证了miR-let-7e的靶基因。检测了Janus激酶1（JAK1）和信号转导及转录激活因子3（STAT3）的表达水平。结果表明，与对照组相比，AR患者和小鼠中miR-let-7e表达下调。此外，与对照组相比，AR小鼠血液中炎症因子的表达水平更高，而miR-let-7e过表达可抑制AR小鼠和IL-13刺激的NECs中这些炎症因子的水平。此外，细胞因子信号转导抑制因子4（SOCS4）被揭示为miR-let-7e的潜在靶基因，并受到miR-let-7e的负调控。SOCS4过表达消除了miR-let-7e过表达的抗炎活性。最后，miR-let-7e过表达激活了JAK1/STAT3信号通路。总之，miR-let-7e可能在AR的进展和发展中起重要作用，而miR-let-7e过表达通过靶向SOCS4发挥抗炎作用，这可能通过激活JAK1/STAT3信号通路来实现。
