LncRNA XIST promotes inflammation by downregulating GRα expression in the adenoids of children with OSAHS

Abstract

Whether glucocorticoid receptor α (GRα) serves a role in obstructive sleep apnea/hypopnea syndrome (OSAHS) remains unclear. However, it has been reported that GRα expression is decreased in the adenoids of patients with OSAHS. The present study aimed to evaluate the role of GRα in OSAHS and the underlying mechanism. Bioinformatics assays revealed that long noncoding RNA (lncRNA) X inactivate-specific transcript (XIST) was closely associated with GRα. Furthermore, reverse transcription-quantitative PCR showed that the expression of lncRNA XIST was significantly increased in the adenoids of patients with OSAHS compared with healthy controls. Further in vitro studies by Pearson correlation analysis, RNA pull-down assay, western blot analysis and ELISA demonstrated that XIST significantly decreased the expression of GRα and that significantly increased the production of inflammatory cytokines, including interleukin (IL)-8, tumor necrosis factor α, IL-6 and IL-1β, while the overexpression of GRα significantly decreased the production of these inflammatory cytokines in NP69 cells, a human nasopharyngeal epithelial cell line. Furthermore, XIST significantly increased the protein levels of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) subunits, including Rel-B, c-Rel, P52, P50 and P65, which are associated with the transcription of cytokines. The stimulatory effect of XIST was significantly inhibited by the NF-κB inhibitor EVP4593. These results indicated that the stimulatory effect of XIST was dependent on NF-κB. In summary, the present study demonstrated that the XIST-GRα-NF-κB signaling pathway contributed to inflammation in the adenoids of patients with OSAHS.