Otorhinolaryngology and Head and Neck Surgery Department, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Hum Exp Toxicol. 2021 Dec;40(12_suppl):S233-S245. doi: 10.1177/09603271211035665. Epub 2021 Aug 18.
Allergic rhinitis (AR) is a type I hypersensitive disease. Long non-coding RNA (lncRNA) SNHG16 acts as an oncogene in a variety of tumors and promotes the occurrence of inflammation in many inflammatory diseases. The study aims to investigate the expression of SNHG16 and its potential biological functions in AR. RT-qPCR results showed that the expression of SNHG16 in AR was up-regulated. The AR cell model was constructed by stimulating primary nasal mucosal epithelial cells from AR patients with IL-13. After knocking down the expression of lncRNA SNHG16, cell apoptosis was detected by flow cytometry, and the expression of inflammatory factors was detected by ELISA. The results showed that SNHG16 promoted cell apoptosis and inflammation. Then, bioinformatics analysis was used to screen miRNAs bound with SNHG16. Luciferase reporter gene assay and RNA pull-down experiment were used to verify the relationship. We found that the expression of miR-106b-5p was down-regulated and leukemia inhibitory factor (LIF) expression was up-regulated in the AR cell model. The expression of phospho-Janus kinase 1 and p-signal transducer and activator of transcription 3 (STAT3) were detected by Western blotting. Silencing the expression of LIF could inhibit the activity of JAK1/STAT3 pathway and further inhibit cell apoptosis and the occurrence of inflammation. Then transfected SNHG16 shRNA alone or together with miR-106b-5p antagomir into the AR cell model, we found that silencing the expression of SNHG16 down-regulated the expression of LIF and inhibited the activity of the JAK1/STAT3 pathway, cell apoptosis, and inflammation. However, miR-106b-5p antagomir weakened its inhibitory effects. The role of SNHG16 in AR was further verified by the ovalbumin-induced AR mouse model . In conclusion, SNHG16 up-regulates LIF expression by binding with miR-106b-5p, thus promoting the activity of JAK1/STAT3 pathway, and promoting the development of AR. These results provide new targets for the treatment of AR and may help reduce the damage caused by AR.
变应性鼻炎（AR）是一种 I 型超敏疾病。长链非编码 RNA（lncRNA）SNHG16 在多种肿瘤中作为癌基因发挥作用，并促进许多炎症性疾病的炎症发生。本研究旨在探讨 SNHG16 在 AR 中的表达及其潜在的生物学功能。RT-qPCR 结果表明，AR 中 SNHG16 的表达上调。通过用白细胞介素 13（IL-13）刺激 AR 患者的原代鼻黏膜上皮细胞构建 AR 细胞模型。敲低 lncRNA SNHG16 的表达后，通过流式细胞术检测细胞凋亡，通过 ELISA 检测炎症因子的表达。结果表明，SNHG16 促进细胞凋亡和炎症。然后，进行生物信息学分析以筛选与 SNHG16 结合的 miRNAs。通过荧光素酶报告基因检测和 RNA 下拉实验验证关系。我们发现，在 AR 细胞模型中，miR-106b-5p 的表达下调，白血病抑制因子（LIF）的表达上调。通过 Western blot 检测磷酸化 Janus 激酶 1（p-JAK1）和信号转导子和转录激活子 3（p-STAT3）的表达。沉默 LIF 的表达可抑制 JAK1/STAT3 通路的活性，进而抑制细胞凋亡和炎症的发生。然后将 SNHG16 shRNA 单独或与 miR-106b-5p antagomir 一起转染入 AR 细胞模型，我们发现沉默 SNHG16 的表达下调了 LIF 的表达并抑制了 JAK1/STAT3 通路的活性、细胞凋亡和炎症。然而，miR-106b-5p antagomir 削弱了其抑制作用。通过卵清蛋白诱导的 AR 小鼠模型进一步验证了 SNHG16 在 AR 中的作用。总之，SNHG16 通过与 miR-106b-5p 结合上调 LIF 的表达，从而促进 JAK1/STAT3 通路的活性，促进 AR 的发展。这些结果为 AR 的治疗提供了新的靶点，并可能有助于减少 AR 造成的损害。
