长链非编码RNA Linc00638的低表达通过调节炎症和氧化应激促进类风湿关节炎进展
[The low expression of long non-coding RNA Linc00638 contributes to rheumatoid arthritis progression by regulating inflammation and oxidative stress].
作者信息
Sun Y, Liu J, Xin L, Zhou Q, Chen X, Ding X, Zhang X
机构信息
Graduate School of Anhui University of Traditional Chinese Medicine, Hefei 230031, China.
Department of Rheumatology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, China.
出版信息
Nan Fang Yi Ke Da Xue Xue Bao. 2021 Jul 20;41(7):965-971. doi: 10.12122/j.issn.1673-4254.2021.07.01.
OBJECTIVE
To investigate the expression of long non-coding RNA (lncRNA) Linc00638 in rheumatoid arthritis (RA) and its regulatory role in inflammation and oxidative stress of synovial fibroblasts in RA patients (RA-FLS).
METHODS
Peripheral blood mononuclear cells (PBMCs) were collected from 20 healthy individuals and 35 RA patients for detecting the expression of Linc00638 using RT-qPCR to analyze the correlation of Linc00638 expression with the clinical indicators of RA patients. A Linc00638 overexpression plasmid and siRNA targeting Linc00638 were transfected into RA-FLS, and the changes in cell viability was observed using CCK8 assay; the changes in the expression levels of interleukin-4 (IL-4), IL-6, reactive oxygen species (ROS) and superoxide dismutase (SOD) in the supernatant were detected using ELISA.
RESULTS
Compared with the healthy control subjects, RA patients had significantly increased ESR, CRP, RF, anti-CCP, IgA, and C4 levels ( < 0.05) and significantly decreased Linc00638 expression in the PBMCs ( < 0.01). The area under the receiver-operating characteristic (ROC) curve of Linc00638 was 91.86% with the best cut-off value of 0.74 for diagnosis of RA. Spearman correlation analysis showed that Linc00638 expression level was negatively correlated with age, course of disease, DAS28, ESR, CRP, RF and anti-CCP, and positively correlated with IL-4 and SOD levels ( < 0.05). Association rule analysis showed that a decreased Linc00638 expression was strongly correlated with an increase of age (>60 years), a longer disease course (>10 years), elevated levels of ESR, RF and anti-CCP, and decreased levels of IL-4 and SOD. In RA-FLS, overexpression of Linc00638 significantly inhibited while Linc00638 interference obviously enhanced the cell viability. Over-expression of Linc00638 also significantly increased the levels of IL-4 and SOD ( < 0.05) and decreased the expressions of IL-6 and ROS ( < 0.05), while interference of Linc00638 produced the opposite effects in the cells ( < 0.05).
CONCLUSION
RA patients have low expression levels of Linc00638, which may participate in disease progression by regulating inflammation and oxidative stress.
目的
探讨长链非编码RNA（lncRNA）Linc00638在类风湿关节炎（RA）中的表达及其对RA患者滑膜成纤维细胞（RA-FLS）炎症和氧化应激的调控作用。
方法
收集20例健康个体和35例RA患者的外周血单个核细胞（PBMCs），采用RT-qPCR检测Linc00638的表达，分析Linc00638表达与RA患者临床指标的相关性。将Linc00638过表达质粒和靶向Linc00638的siRNA转染至RA-FLS，采用CCK8法观察细胞活力变化；采用ELISA检测上清液中白细胞介素-4（IL-4）、IL-6、活性氧（ROS）和超氧化物歧化酶（SOD）表达水平的变化。
结果
与健康对照者相比，RA患者的ESR、CRP、RF、抗CCP、IgA和C4水平显著升高（<0.05），PBMCs中Linc00638表达显著降低（<0.01）。Linc00638的受试者工作特征（ROC）曲线下面积为91.86%，诊断RA的最佳截断值为0.74。Spearman相关性分析显示，Linc00638表达水平与年龄、病程、DAS28、ESR、CRP、RF和抗CCP呈负相关，与IL-4和SOD水平呈正相关（<0.05）。关联规则分析显示，Linc00638表达降低与年龄增加（>60岁）、病程延长（>10年）、ESR、RF和抗CCP水平升高以及IL-4和SOD水平降低密切相关。在RA-FLS中，Linc00638过表达显著抑制细胞活力，而Linc00638干扰则明显增强细胞活力。Linc00638过表达还显著提高IL-4和SOD水平（<0.05），降低IL-6和ROS表达（<0.05），而Linc00638干扰则在细胞中产生相反的作用（<0.05）。
结论
RA患者Linc00638表达水平较低，其可能通过调节炎症和氧化应激参与疾病进展。
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