LncRNA NEAT1通过调节miR-124-3p/KLF4轴改善过敏性鼻炎  

Long non-coding RNA NEAT1 modulates allergic rhinitis via regulating miR-124-3p/KLF4 axis

作　　者：梁红宇 任宇 刘晓佳 王潇 刘晓玲 LIANG Hongyu;RNE Yu;LIU Xiaojia;WANG Xiao;LIU Xiaoling(Office of Academic Research,Inner Mongolia People’s Hospital,Hohhot 010017,China)

机构地区：[1]内蒙古自治区人民医院科研处,呼和浩特010017

出　　处：《中华临床免疫和变态反应杂志》2024年第2期137-147,共11页Chinese Journal of Allergy & Clinical Immunology

基　　金：内蒙古自治区科技计划项目(2020GG0082);内蒙古自治区自然科学基金项目(2022QN08030);内蒙古自治区卫生健康委科技计划项目(202201068)。

摘　　要：目的长链非编码RNA(long non-coding RNA,lncRNA)已被证明在过敏性鼻炎(allergic rhinitis,AR)发展中发挥重要作用。本研究旨在探究lncRNA NEAT1(nuclear enriched abundant transcript 1)在AR中的功能和分子机制。方法构建了卵清白蛋白(ovalbumin,OVA)诱导的AR小鼠模型和IL-13诱导的人鼻上皮细胞(human nasal epithelial cells,HNECs)模型。结果NEAT1在AR小鼠体内高表达。敲低NEAT1显著抑制了AR小鼠和HNECs中炎性因子的产生,并减少了细胞凋亡。进一步的研究表明,NEAT1的下调能够逆转miR-124-3p的上调和KLF4的下调,进而调节了IL-13诱导的HNECs中的炎性反应和细胞凋亡。此外,miR-124-3p过表达显著提高了HNECs细胞活力,抑制了细胞凋亡、炎症因子的产生和KLF4的表达。而NEAT1过表达显著逆转了这一现象。结论本研究发现NEAT1在AR中的高表达,并揭示了其通过miR-124-3p/KLF4信号通路调控炎性反应和细胞凋亡的机制。这些发现不仅为深入理解AR的分子机制提供了新的视角,还为进一步研究和治疗AR提供了潜在的靶点。Objective Long non-coding RNA(lncRNA)had been confirmed to play a crucial role in development of allergic rhinitis(AR).The aim of this study is to investigate function and molecular mechanism of lncRNA Nuclear Enriched Abundant Transcript 1(NEAT1)in pathogenesis of AR.Methods Ovalbumin(OVA)-induced AR mouse model and IL-13-induced human nasal epithelial cells(HNECs)model were established.Results NEAT1 was highly expressed in AR mice.Production of inflammatory factors were significantly inhibited by knock-down of NEAT1 in AR mice and HNECs,as well as reduction of cell apoptosis.Results of further research demonstrated that up-regulation of miR-124-3p and down-regulation of Krüppel-like factor 4(KLF4)could be reversed by down-regulation of NEAT1,thereby inflammatory responses and cell apoptosis in IL-13-induced HNECs were also regulated.In addition,overexpression of miR-124-3p resulted in significant improvement of viability of HNEC cells,inhibition of cell apoptosis and production of inflammatory factors,as well as expression of KLF4.However,phenomenon mentioned above could be significantly reversed by overexpression of NEAT1.Conclusions High expression of NEAT1 in AR was demonstrated in this study,revealing mechanism of its regulatory function on inflammatory response and cell apoptosis through miR-124-3p/KLF4 signaling pathway.These findings not only provided new perspective for in-depth understanding of molecular mechanism of AR,but also proffered potential targets for further research and treatment of AR.

关 键 词：过敏性鼻炎 LncRNA NEAT1 miR-124-3p KLF4 

分 类 号：R765.21[医药卫生—耳鼻咽喉科]