Increased expression of microRNA-338-3p contributes to production of Dsg3 antibody in pemphigus vulgaris patients.

Abstract

Expression of microRNA-338-3p (miR-338-3p) was aberrantly elevated in pemphigus vulgaris (PV), although its role in PV is still unknown. The present study investigated the functional role and possible molecular mechanisms of miR-338-3p in PV. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect miR-338-3p expression in peripheral blood mononuclear cells (PBMCs) from patients with PV. Correlation with disease severity and anti-desmoglein3 antibody (anti-Dsg3) titers were analyzed in patients with PV. The effects of overexpression and knockdown of miR-338-3p expression in PBMCs and effects on Th1 and Th2 cytokines were also examined using ELISA. The luciferase reporter analysis, RT-qPCR and western blot analysis were applied to investigate potential and functional target genes. The data showed that miR-338-3p expression was significantly upregulated in PV and the upregulation of miR-338-3p associated with disease severity and a high anti-Dsg3 antibody titer. Expression of miR-338-3p/mimic in healthy PBMCs significantly downregulated Th1 cytokine (IFN-γ) and upregulated Th2 cytokines (IL-4 and IL-10), whereas knockdown of miR-338-3p expression in PBMCs from patients with PV induced the reverse effects. Overexpression of miR-338-3p suppressed cell viability. Luciferase reporter, RT-qPCR and western blot assays idnicated that TNFR1-associated death domain protein (TRADD) was the direct and functional target of miR-338-3p. Increased expression of miR-338-3p contributed to the production of Dsg3 antibody by inhibiting TRADD expression to induce an imbalance in Th1/Th2 cell functions. Taken together, this study suggests that miR-338-3p may be used as a potential therapeutic target for PV treatment.