Department of Rheumatology and Immunology at Shengjing Hospital of China Medical University, Shenyang, China.
Department of Orthopedics at Shengjing Hospital of China Medical University, Shenyang, China.
Front Immunol. 2020 Aug 28;11:1975. doi: 10.3389/fimmu.2020.01975. eCollection 2020.
LncRNA NEAT1 functions as an oncogene in multiple human cancers. However, its expression and role in fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) remain unclear. Thus, we investigated the expression of NEAT1 in synovial tissues and FLSs in RA, to determine its role in the development of RA. Quantitative real-time polymerase chain reaction was used to measure the expression of NEAT1. FLS proliferation was evaluated using cell proliferation assays. Flow cytometry was used to analyze cell cycle progression and apoptosis in FLSs. Binding between NEAT1 and miR-410-3p was demonstrated by dual-luciferase assays. We found that NEAT1 was upregulated in synovial tissues and FLSs in RA. Upregulation of NEAT1 promoted cell proliferation, induced S-to G2/M phase transition, and suppressed apoptosis in RA FLSs. NEAT1 directly bound to and negatively modulated miR-410-3p expression, while positively regulating YinYang 1(YY1; a miR-410-3p target). Inhibiting miR-410-3p and upregulating YY1 partially restored the inhibitory role in cell viability induced by the depletion of NEAT1 in RA FLSs. Besides pro-proliferative and anti-apoptotic roles, upregulation of NEAT1 promoted migration, invasion, and inflammatory cytokines secretion in RA FLSs. Taken together, our results suggest that the NEAT1 may serve as a novel diagnostic and therapeutic target for patients with RA.
LncRNA NEAT1 在多种人类癌症中作为癌基因发挥作用。然而，其在类风湿关节炎（RA）患者成纤维样滑膜细胞（FLSs）中的表达和作用尚不清楚。因此，我们研究了 NEAT1 在 RA 滑膜组织和 FLSs 中的表达，以确定其在 RA 发病机制中的作用。采用实时定量聚合酶链反应（qRT-PCR）检测 NEAT1 的表达。通过细胞增殖实验评估 FLSs 的增殖情况。采用流式细胞术分析 FLSs 的细胞周期进程和凋亡。通过双荧光素酶报告基因实验证实 NEAT1 与 miR-410-3p 之间的结合。结果发现，NEAT1 在 RA 滑膜组织和 FLSs 中呈上调表达。上调 NEAT1 促进 RA FLSs 增殖，诱导 S 期至 G2/M 期过渡，并抑制细胞凋亡。NEAT1 可直接与 miR-410-3p 结合并负调控其表达，同时正向调控 YinYang 1（YY1；miR-410-3p 的靶基因）。抑制 miR-410-3p 并上调 YY1 可部分恢复 NEAT1 耗竭对 RA FLSs 细胞活力的抑制作用。除了具有促增殖和抗凋亡作用外，上调 NEAT1 还可促进 RA FLSs 的迁移、侵袭和炎性细胞因子分泌。综上，我们的研究结果表明，NEAT1 可能成为 RA 患者的一种新型诊断和治疗靶点。
