环状RNA circ_0008668调控miR-6089影响下游TLR4通路对变应性鼻炎的作用机制研究

变应性鼻炎（AR）的发生发展受遗传和环境因素交互作用的影响。申请者在前期工作中建立了AR患者鼻黏膜组织差异表达的circRNA-microRNA-mRNA构成的竞争性内源RNA（ceRNA）三维网络，初步发现环状RNA circ_0008668在AR中表达差异明显。根据生物信息学分析，miR-6089可分别与circ_0008668和TLR4结合。已有研究表明miR-6089可直接作用于TLR4，从而抑制TLR4的表达。然而circ_0008668作为ceRNA在AR发病中的机制尚不清楚。本项目拟在此基础上，深入分析探讨circ_0008668与AR的相关性；同时，在体外细胞和动物模型实验中进一步研究circ_0008668在AR发病中的调控机制，解析下游效应途径及靶点，阐明circ_0008668调控miR-6089影响下游TLR4通路对AR的作用机制，为未来AR的精准治疗提供新思路。

The occurrence and development of allergic rhinitis (AR) are influenced by the interaction of genetic and environmental factors. In our previous work, we established a three-dimensional network of competitive endogenous RNA (ceRNA) composed of circRNA-microRNA-mRNA differentially expressed in nasal mucosa of AR patients. It was preliminarily found that the expression of circular RNA circ_0008668 in AR was significantly different. According to bioinformatics analysis, miR-6089 can bind to circ_0008668 and TLR4, respectively. Previous studies have shown that miR-6089 can directly act on TLR4, thus inhibiting the expression of TLR4. However, the mechanism of circ_0008668 acting as a ceRNA in the pathogenesis of AR remains unclear. On this basis, this study intends to deeply analyze and explore the correlation between circ_0008668 and AR. Meanwhile, through cell and animal model experiments, we will further study the regulative mechanism of circ_0008668 in AR pathogenesis, analyze the downstream effect pathways and targets to clarify the mechanism that circ_0008668 regulate AR via competitively binding miR-6089 with TLR4 pathway, and provide new ideas for the precise medicine of AR in future.