Jianhua Wu,1,2 Yisha Wu,1 Peng Jin,3 Xiaoxue Zi,3 Yuzhu Wan,1 Kaiyue Sun,1,4 Li Shi,1,3 Deyun Wang5 

1Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Otolaryngology Head and Neck Surgery, Binzhou People’s Hospital, Binzhou, Shandong, People’s Republic of China; 3Department of Otolaryngology, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 4Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 5Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

Correspondence: Li Shi, Department of Otolaryngology, The Second Hospital of Shandong University, Jinan, Shandong, 250033, People’s Republic of China, Tel +86 0531 83086278, Fax +86 0531 83086279, Email shili126@sina.com Kaiyue Sun, Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250022, People’s Republic of China, Tel +86 0531 83086277, Fax +86 0531 83086279, Email 18354159626@163.com

Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.

Keywords: allergic rhinitis, hsa_circ_100791, miR-487b-5p, Trim13, diagnosis, inflammation, NF-κB