Hsa_circRNA_100791 Modulates Trim13 Through Sponging miR-487b-5p to Facilitate Inflammation in Allergic Rhinitis

J Inflamm Res. 2024 Dec 17:17:11175-11193. doi: 10.2147/JIR.S485165. eCollection 2024.

Abstract

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: NF-κB; Trim13; allergic rhinitis; diagnosis; hsa_circ_100791; inflammation; miR-487b-5p.

Grants and funding

This work was supported by the National Nature Science Foundation of China (82371117; Li Shi) and Key R & D Program of Shandong Province (2018CXGC1214; Li Shi), the National Nature Science Foundation of China (82101195; Xiaoxue Zi).