Conclusion
miR-6089 can alleviate LPS-induced inflammatory response via targeting TLR4 and may serve as a therapeutic target in the treatment of mite-sensitized AR.
Methods
Nasal mucosa was collected from patients with mite-sensitized AR and non-allergic controls for miRNA and mRNA sequencing. miRNA expression was profiled. GO and KEGG enrichment analyses were conducted. Luciferase reporter assay was implemented to identify potential targets of candidate miRNAs. An AR cell model was established through lipopolysaccharide (LPS) exposure. miR-6089 was overexpressed or downregulated to characterize its roles in the proliferation and apoptosis of human nasal epithelial cells (HNEpC). The relationship between miR-6089 and toll-like receptor 4 (TLR4) was described. PCR and ELISA were applied to quantify the expression levels of miRNAs and mRNAs.
Purpose
Allergic rhinitis (AR), a chronic inflammatory disease of nasal mucosa, is considered as a classic Th2-mediated disease. We aimed to elucidate the molecular mechanisms and therapeutic potential of microRNAs (miRNAs) in AR.
Results
A total of 28 miRNAs and 172 mRNAs were identified to be differently expressed in the nasal mucosa of patients with AR compared to controls. The KEGG enrichment analysis showed that TLR signaling pathway, NF-κB signaling pathway, IL-17 signaling pathway and other pathways were significantly enriched in these differentially expressed RNAs. As shown by PCR results, the expression of miR-6089 decreased, and that of TLR4, IL-6, IL-8, and TSLP increased significantly in the nasal mucosa from patients with AR. Dual-luciferase reporter assay showed that miR-6089 directly bound to TLR4. miR-6089 could increase the viability, inhibit apoptosis, and relieve inflammatory response in LPS-induced HNEpC. Furthermore, miR-6089 could regulate the expression of TLR4, IL-6, IL-8, and TSLP in the LPS-induced HNEpC.