Ding Xiang, Liu Jian, Sun Yanqiu
Graduate School, Anhui University of Traditional Chinese Medicine, Hefei, Anhui 230031, P.R. China.
Institute of Rheumatology, Anhui University of Chinese Medicine, Hefei, Anhui 230012, P.R. China.
Exp Ther Med. 2023 Mar 31;25(5):231. doi: 10.3892/etm.2023.11930. eCollection 2023 May.
Long non-coding RNAs (lncRNAs) assume pivotal roles in various autoimmune diseases including ankylosing spondylitis (AS). Inflammation affects the progression of multiple diseases. The current research aimed at dissecting out the possible role and mechanism of lncRNAs NONHSAT227927.1 in the pathogenesis of AS. In clinical trials, 50 patients with AS and 30 healthy persons were enrolled, followed by the extraction of peripheral blood mononuclear cells (PBMCs). NONHSAT227927.1 expression was detected using reverse transcription quantitative PCR. Enzyme-linked immunosorbent assay was used to determine the levels of inflammatory cytokines. Human fibroblast-like synoviocytes (FLSs) were induced by PBMC supernatant, after which the activity of FLSs was measured by Cell Counting Kit-8 and the signaling pathway were detected by western blotting. Cell migratory capacity was assessed by Transwell migration assay. NONHSAT227927.1 expression was obviously enhanced in the PBMCs of AS patients. NONHSAT227927.1 expression was positively correlated with immunoglobin A (IgA), erythrocyte sedimentation rate (ESR), complement C3 (C3), visual analog scale, IL-17, and IL-23 Levels but was negatively correlated with IL-10 level. The results of association rules showed that the increase of NONHSAT227927.1 expression was strongly associated with the elevation of IgA, C3, ESR, self-rating anxiety scale and IL-17 levels. Overexpression of NONHSAT227927.1 remarkably augmented the proliferation and migration of AS-PBMCs stimulated by AS-FLSs, facilitated the levels of IL-17 and IL-23, and reduced the IL-10 level. By contrast, NONHSAT227927.1 knockdown decreased cell proliferation and migration and cell viability as well as the levels of IL-17 and IL-23, but increased the level of IL-10. overexpression of NONHSAT227927.1 promoted the phosphorylation of JAK2 and STAT3 proteins, while knockout of NONHSAT227927.1 decreased their phosphorylation. Conclusively, lncRNA NONHSAT227927.1 was overexpressed in AS, which activated the JAK2/STAT3 signaling pathway to upregulate inflammatory factors.
长链非编码RNA(lncRNAs)在包括强直性脊柱炎(AS)在内的多种自身免疫性疾病中发挥着关键作用。炎症影响多种疾病的进展。当前研究旨在剖析lncRNAs NONHSAT227927.1在AS发病机制中的可能作用及机制。在临床试验中,纳入了50例AS患者和30名健康人,随后提取外周血单个核细胞(PBMCs)。使用逆转录定量PCR检测NONHSAT227927.1的表达。采用酶联免疫吸附测定法测定炎性细胞因子水平。用PBMC上清液诱导人成纤维样滑膜细胞(FLSs),之后通过细胞计数试剂盒-8检测FLSs的活性,并通过蛋白质印迹法检测信号通路。通过Transwell迁移试验评估细胞迁移能力。AS患者PBMCs中NONHSAT227927.1的表达明显增强。NONHSAT227927.1的表达与免疫球蛋白A(IgA)、红细胞沉降率(ESR)、补体C3(C3)、视觉模拟评分、IL-17和IL-23水平呈正相关,但与IL-10水平呈负相关。关联规则结果显示,NONHSAT227927.1表达的增加与IgA、C3、ESR、自评焦虑量表和IL-17水平的升高密切相关。NONHSAT227927.1的过表达显著增强了AS-FLSs刺激的AS-PBMCs的增殖和迁移,促进了IL-17和IL-23的水平,并降低了IL-10水平。相比之下,敲低NONHSAT227927.1可降低细胞增殖、迁移和细胞活力以及IL-17和IL-23的水平,但增加了IL-10的水平。NONHSAT227927.1的过表达促进了JAK2和STAT3蛋白的磷酸化,而敲除NONHSAT227927.1则降低了它们的磷酸化。总之,lncRNA NONHSAT227927.1在AS中过表达,激活JAK2/STAT3信号通路以上调炎性因子。