X-inactive specific transcript provides a novel biomarker in Behçet’s uveitis and modulates retinal epithelial cell biological function via sponging miR-27a-3p

Abstract: PURPOSE: Behçet’s uveitis (BU) is a chronic, recurrent and potentially blinding inflammatory disease. This study aims to explore the X-inactive specific transcript (XIST) as a novel biomarker for BU, and to clarify the mechanism by which it regulates the function of retinal epithelial cells (ARPE-19) through sponging miR-27a-3p. METHODS: We enrolled 35 patients with BU and 30 healthy controls (HC), and collected peripheral venous blood samples. The levels of XIST and miR-27a-3p were determined by quantitative real-time polymerase chain reaction, and the clinical value of XIST was verified through the receiver-operating characteristic curves. The interaction between XIST and miR-27a-3p in BU was confirmed by the dual luciferase reporter gene assay. The BU model was established by jointly treating ARPE-19 cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-γ). The levels of inflammatory factors were analyzed by enzyme-linked immunosorbent assay. The cell viability and apoptosis were detected using cell counting kit 8 and flow cytometry. RESULTS: Patients with BU had significantly higher levels of XIST compared to HC. XIST has certain specificity and sensitivity and can distinguish BU patients from healthy individuals. The target molecule miR-27a-3p of XIST was significantly decreased in BU patients. In addition, the treatments with LPS and IFN-γ can inhibit cell proliferation, promote cell apoptosis, and stimulate the production of inflammatory factors. However, si-XIST could significantly inhibit the effects of LPS and IFN-γ, but this inhibitory effect was significantly weakened when miR-27a-3p was reduced. CONCLUSION: XIST may be a potential biomarker for diagnosing BU. XIST can inhibit the anti-inflammatory function of miR-27a-3p through sponge adsorption, thereby exacerbating the damage and inflammatory response of ARPE-19 cells.