LncRNA Neat1 positively regulates MAPK signaling and is involved in the pathogenesis of Sjögren's syndrome

Abstract Objective Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands. Recent, studies have shown that the long noncoding RNA (lncRNA) NEAT1 plays a crucial role in regulating the immune response. However, studies on the lncRNA NEAT1 in pSS are limited. Exploring the role of the lncRNA NEAT1 in the pathogenesis of pSS was the purpose of this study. Methods The expression of NEAT1 in peripheral blood mononuclear cells (PBMCs) of patients with pSS and healthy controls (HCs) was analyzed by real-time polymerase chain reaction (RT-PCR). Antisense oligonucleotides (ASOs) and siRNA or immune stimulation with PMA/ionomycin were used to perform loss-and-gain-of-function experiments. RT-PCR, enzyme-linked immunosorbent assay (ELISA), and Western blot were performed to detect the RNA and protein levels of specific genes induced by PMA/ionomycin stimulation. Microarray analysis was used to generate an overview of the genes that might be regulated by NEAT1. Results Compared with that in HC patient cells, the expression of NEAT1 in pSS patients was mainly increased in peripheral T cells, including CD4+ and CD8+ T cells. Additionally, the expression of NEAT1 in CD4+ T cells of patients with pSS was positively correlated with the course of disease. NEAT1 expression in Jurkat cells was induced by PMA/ionomycin stimulation upon activation of the TCR-p38 pathway. Upregulation of NEAT1 expression also increased the expression of CXCL8 and TNF-α. Knocking down NEAT1 expression with an ASO suppressed the expression of CXCL8 and TNF-α in PMA/ionomycin-stimulated Jurkat cells. Then, we found that NEAT1 regulated the activation of MAPK pathway to regulate NEAT1-induced factors, selectively activating the expression of p-p38 and p-ERK1/2. Furthermore, we also detected the expression profile of Jurkat cells stimulated by PMA/ionomycin when NEAT1 was silenced or not, in order to produce an overview of NEAT1-regulated genes. Conclusion These results provide a new understanding of the mechanisms of pSS and reveal that NEAT1 is a positive regulator of pSS, which is of substantial significance to its pathogenesis. Thus, NEAT1 provides a potential therapeutic target for pSS.