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Dicer 在类风湿关节炎中的表达与疾病活动度相关,并平衡 TNF-α 的产生。

Expression of Dicer in rheumatoid arthritis is associated with disease activity and balances the production of TNF‑α.

机构信息

Department of Rheumatology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.

Department of Rheumatology, People's Hospital of Liaocheng, Liaocheng, Shandong 252002, P.R. China.

出版信息

Mol Med Rep. 2017 Aug;16(2):1590-1595. doi: 10.3892/mmr.2017.6746. Epub 2017 Jun 9.

Abstract

Gene expression can be altered through RNA interference (RNAi), including microRNA (miRNA) or small interfering RNA. Alterations of miRNAs in rheumatoid arthritis (RA) have been reported, however, the components of the RNAi machinery in RA remain to be fully elucidated. The aim of the present study was to detect the levels of Dicer, Argonaute2 and Drosha, components of the RNAi machinery, in the peripheral blood mononuclear cells of patients with RAusingreverse transcription‑quantitative polymerase chain reaction, and to compare the results with disease activity and clinical features. Disease activity was assessed using the Disease Activity Score 28 (DAS28). Transfection and stimulation of cultured cells were conducted to determine the biological function of Dicer. ELISA was used to test tumor necrosis factor (TNF)‑α protein levels. It was found that the mRNA expression levels of Dicer and Drosha were upregulated in patients with RA, and that the increased level of Dicer was correlated with disease activity in patients with RA. Dicer and TNF‑α were activated in the serum of patients with RA. The activation of Dicer suppressed the production of TNF‑α. These results suggested that Dicer can balance the production of TNF‑α, and thus may serve as a regulator of the immune response in patients with RA.

摘要

基因表达可以通过 RNA 干扰(RNAi)进行改变,包括 microRNA(miRNA)或小干扰 RNA。已经报道了类风湿关节炎(RA)中 miRNA 的改变,然而,RA 中 RNAi 机制的组成部分仍有待充分阐明。本研究的目的是使用逆转录-定量聚合酶链反应检测 RA 患者外周血单个核细胞中 RNAi 机制的组成部分 Dicer、Argonaute2 和 Drosha 的水平,并将结果与疾病活动度和临床特征进行比较。使用疾病活动评分 28(DAS28)评估疾病活动度。进行转染和培养细胞刺激以确定 Dicer 的生物学功能。使用 ELISA 检测肿瘤坏死因子(TNF)-α 蛋白水平。结果发现,RA 患者的 Dicer 和 Drosha mRNA 表达水平上调,并且 Dicer 的增加水平与 RA 患者的疾病活动度相关。Dicer 和 TNF-α 在 RA 患者的血清中被激活。Dicer 的激活抑制了 TNF-α 的产生。这些结果表明,Dicer 可以平衡 TNF-α 的产生,因此可能作为 RA 患者免疫反应的调节剂。

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