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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.

SUBMITTER: Zhou Z

PROVIDER: S-EPMC8005745 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Obstructive sleep apnea-hypopnea syndrome (OSAHS) is prone to being complicated with various cardiovascular, cerebrovascular and metabolic conditions. OSAHS, due to its multifactorial nature, entails individualized and comprehensive treatment. So far, no well-established diagnostic criteria for the disease are available. In recent years, miRNA has been shown to be a sensitive biomarker suggestive of the progression and prognosis of many diseases. In this study, we examined some serum miRNAs in healthy OSAHS (OSAHS patients without complication) and OSAHS with arterial hypertension, with an attempt to understand the potential effects on the disease, improve the diagnosis of OSAHS and find OSAHS-related diagnostic markers. METHODS:Against various diagnostic criteria, participants were divided into three groups: healthy OSAHS, OSAHS with arterial hypertension and healthy controls. Their serum miRNA profiles were assessed by microarray technology, and then differentially expressed miRNAs were verified by quantitative real-time PCR (qRT-PCR). The receiver operating characteristic (ROC) curves of miRNAs were constructed and the areas under the curve (AUC) were calculated. Meanwhile, the miRNAs were subjected to logistic regression analysis. The target genes were bioinformatically assessed, their functions and signaling pathways further determined and eventually an miRNA-gene network was established. RESULTS:Analysis with the miRNA array exhibited that, compared with the control group, 12 differentially expressed miRNAs were found in healthy OSAHS, and 33 were found in OSAHS with arterial hypertension. The expression of miR-126-3p, let-7d-5p, miR-7641 and miR-1233-5p, miR-320b, miR-145-5p, miR-107, miR-26a-5p were validated by using qRT-PCR. Bioinformatics analysis predicted that the potential target genes of these miRNAs might be involved in metabolism, and the regulation of endothelial cells and nervous system. Moreover, the ROC analysis showed that the using miR-145-5p and let-7d-5p in combination can identify the healthy OSAHS, presence of miR-126-3p, miR-26a-5p and miR-107 was well indicative of OSAHS with arterial hypertension. CONCLUSIONS:A cluster of dysregulation miRNAs have been found to be involved in the development of OSAHS patients. Moreover, these miRNAs might be used to be potential diagnostic and early warning markers.

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

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