Exosomal lncRNA Nuclear Paraspeckle Assembly Transcript 1 (NEAT1)contributes to the progression of allergic rhinitis via modulating microRNA-511/Nuclear Receptor Subfamily 4 Group A Member 2 (NR4A2) axis

Abstract

Allergic rhinitis (AR) is a common chronic disease characterized by inflammation of the nasal mucosa. Long non-coding RNA (LncRNA) has been reported to be involved in the pathogenesis of various diseases. However, the biological roles of lncRNA Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) in AR are still unclear. The mRNA levels of NEAT1, miR-511, and Nuclear Receptor Subfamily 4 Group A Member 2 (NR4A2) were detected by RT-qPCR. The protein levels of exosomal markers were examined by western blot. ELISA was used to assess the levels of GM-CSF, eotaxin-1, and MUC5AC. The cell viability and apoptosis were evaluated by CCK-8 and TUNEL assays. In this study, we found that the NEAT1 level was highly expressed in AR and IL-13-treated HNECs. NEAT1 interference significantly suppressed levels of GM-CSF, eotaxin-1, and MUC5AC and apoptosis rate, but promoted the viability of IL-13-treated human nasal epithelial cells (HNECs). Moreover, exosomes containing NEAT1 induced inflammatory cytokine production and apoptosis, while NEAT1 depletion abrogated these effects. In addition, NEAT1 directly interacted with miR-511, and the inhibition of miR-511 partially restored the inhibitory effects of NEAT1 silencing on inflammatory cytokine, mucus production, and apoptosis in IL-13-stimulated HNECs. Furthermore, miR-511 could bind to the 3ʹUTR of NR4A2, and the inhibition of miR-511 increased levels of inflammatory factors and apoptosis rate, which was counteracted by depleting NR4A2. In conclusion, our data revealed that exosomal NEAT1 contributed to the pathogenesis of AR through the miR-511/NR4A2 axis. These findings might offer novel strategies for the prevention and treatment of AR.

Noncoding RNAs and Virus and Treatment in Allergic Rhinitis

“…Up-regulated miR-511 NR4A2 and IL13 NEAT1 induced inflammatory cytokine production and apoptosis contributing to the pathogenesis of AR via the miR-511/NR4A2 axis [48].…”

Downregulation of lncRNA CDKN2B-AS1 attenuates inflammatory response in mice with allergic rhinitis by regulating miR-98-5p/SOCS1 axis

“…The lncRNA/miRNA/mRNA axis is fully evidenced as the major regulatory mechanism of lncRNAs in multiple diseases, including AR (Wang et al 2021 ). Previous study has demonstrated that CDKN2B-AS1 can act as a ceRNA for miRNAs to mediate cellular processes (Guo et al 2018 ).…”

Aberrant expressions of circulating lncRNA NEAT1 and microRNA‐125a are linked with Th2 cells and symptom severity in pediatric allergic rhinitis

“…(4) The lnc‐NEAT1 expression might be related to exacerbated allergic response via inducing the secretion of pro‐inflammatory cytokines and stimulating inflammatory responses; thus, the lnc‐NEAT1 expression was positively related to the disease severity of pediatric AR patients. 14 , 39 …”