Construction and validation of a lncRNA/circRNA-miRNA-mRNA ceRNA network in allergic rhinitis pathogenesis

The lncRNA/circRNA-miRNA-mRNA interaction constructs a competing endogenous RNAs (ceRNAs) network, which is closely related to inflammation. However, their roles in allergic rhinitis (AR) remain unclear. In this study, we investigated the regulatory role of ceRNA networks in AR pathogenesis by analyzing long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), then constructing a lncRNA/circRNA-miRNA-mRNA interaction network.

An AR mouse model was established using ovalbumin (OVA). Pathological examination was performed on the nasal mucosa of the mice, and ELISA was conducted on the mouse serum. High-throughput sequencing was used to analyze the expression profiles of lncRNAs, circRNAs, miRNAs, and mRNAs in the nasal mucosa of AR mice. A fold change > 2 and a q-value < 0.05 were used to identify the significantly differentially expressed (DE) lncRNAs, circRNAs, miRNAs, and mRNAs in AR. Then, bioinformatics and statistical methods were used to construct ceRNA networks, while RT-PCR was employed to validate RNA seq results.

A total of 216 mRNAs, 241 lncRNAs, 659 circRNAs, and 19 miRNAs were identified as significantly differentially expressed. Among them, 145 mRNAs were up-regulated and 71 were down-regulated; 138 lncRNAs were up-regulated and 103 were down-regulated; 304 circRNAs were up-regulated and 355 were down-regulated; 16 miRNAs were up-regulated and 3 were down-regulated. Additionally, 223 miRNA -mRNA pairs, 50 miRNA-lncRNA pairs, and 17 circRNA-miRNA pairs were obtained, and a network diagram of lncRNA/circRNA-miRNA-mRNA pairs was drawn. Functional enrichment analysis based on the ceRNA network confirmed that lncRNAs are involved in the regulation of the Wnt signaling pathway, ECM-receptor interaction, and the PI3K-Akt signaling pathway. In contrast, circRNAs are implicated in the modulation of adipocyte lipolysis, as well as ECM-receptor interactions and protein digestion and absorption. Some DE-lncRNAs and DE-mRNAs determined by RNA sequencing were verified by RT-PCR, and their trends were similar to those observed in RNA seq.

We established a ceRNA network based on lncRNA/circRNA-miRNA-mRNA interactions for AR, providing a solid foundation for future investigations into its underlying molecular mechanisms and the identification of novel drug targets.