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Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.
Department of Otolaryngology Head and Neck Surgery, Binzhou People's Hospital, Binzhou, Shandong, People's Republic of China.
J Inflamm Res. 2024 Dec 17;17:11175-11193. doi: 10.2147/JIR.S485165. eCollection 2024.
Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNA molecules in eukaryotes, involved in many essential biological processes. However, their role in allergic rhinitis (AR) has not been extensively studied.
The expression levels of hsa_circRNA_100791 were measured using qRT-PCR in peripheral blood mononuclear cells (PBMCs) and nasal mucosa from AR patients. The biological function of hsa_circRNA_100791 in AR was investigated through RNA-seq and a series of in vitro experiments. Western blotting, luciferase reporter assays, and rescue experiments were conducted to elucidate the molecular mechanisms underlying hsa_circRNA_100791. Additionally, a mouse model was used to assess the functional role of hsa_circRNA_100791 in vivo.
Upregulation of hsa_circRNA_100791 was observed in both PBMCs and nasal mucosa of AR patients. In vitro, increased expression of hsa_circRNA_100791 promoted the production of pro-inflammatory mediators (IL-1β, IL-4, IL-5, IL-6, IL-8, IL-13, IL-17, IL-18, IL-33, TNF-α, and NF-κB) and inhibited IL-2 and IFN-γ. Conversely, knockdown of hsa_circRNA_100791 both in vitro and in vivo alleviated AR symptoms, reduced pro-inflammatory mediators, and enhanced IL-2 and IFN-γ levels. Mechanistically, we found hsa_circRNA_100791 contributing to the pathological processes of AR, which upregulate TRIM13 via sponging miR-487b-5p.
Our study demonstrated that hsa_circRNA_100791 mitigates the inhibitory effect of miR-487b-5p on Trim13 by directly binding to miR-487b-5p. This interaction regulates the expression of inflammatory factors and facilitates AR. Thus, hsa_circRNA_100791 could be a promising new therapeutic target for AR.
环状RNA（circRNAs）是真核生物中一类新型的内源性非编码RNA分子，参与许多重要的生物学过程。然而，它们在变应性鼻炎（AR）中的作用尚未得到广泛研究。
采用qRT-PCR检测AR患者外周血单个核细胞（PBMCs）和鼻黏膜中hsa_circRNA_100791的表达水平。通过RNA测序和一系列体外实验研究hsa_circRNA_100791在AR中的生物学功能。进行蛋白质免疫印迹、荧光素酶报告基因检测和拯救实验以阐明hsa_circRNA_100791的分子机制。此外，使用小鼠模型评估hsa_circRNA_100791在体内的功能作用。
在AR患者的PBMCs和鼻黏膜中均观察到hsa_circRNA_100791上调。在体外，hsa_circRNA_100791表达增加促进促炎介质（IL-1β、IL-4、IL-5、IL-6、IL-8、IL-13、IL-17、IL-18、IL-33、TNF-α和NF-κB）的产生，并抑制IL-2和IFN-γ。相反，在体外和体内敲低hsa_circRNA_100791均可减轻AR症状，减少促炎介质，并提高IL-2和IFN-γ水平。机制上，我们发现hsa_circRNA_100791通过海绵吸附miR-487b-5p上调TRIM13，从而参与AR的病理过程。
我们的研究表明，hsa_circRNA_100791通过直接与miR-487b-5p结合减轻miR-487b-5p对Trim13的抑制作用。这种相互作用调节炎症因子的表达并促进AR。因此，hsa_circRNA_100791可能是AR一个有前景的新治疗靶点。
