类风湿关节炎患者血浆miR-146a表达及基因高甲基化与疾病活动程度的关系-东南大学学报医学版

类风湿关节炎患者血浆miR-146a表达及基因高甲基化与疾病活动程度的关系

单位：空军军医大学第一附属医院临床免疫科, 陕西西安 710032

分类号：R593.22

出版年·卷·期（页码）：2022·41·第六期（818-824）

摘要：

目的: 探讨类风湿关节炎(RA)患者血浆微小RNA(miRNA)-146a表达及基因高甲基化与疾病活动程度的关系。方法: 2019年3月至2020年4月在我院临床免疫科招募122例RA患者为RA组,基于血细胞沉降率(ESR)获得28个关节疾病活动评分(DAS28-ESR)测量疾病活动性;另纳入同期健康志愿者141例为对照组。采用实时荧光定量PCR法检测血浆miR-146a水平,实时荧光定量甲基化特异性PCR(qMSP)分析甲基化状态。结果: RA组患者血浆miR-146a水平显著高于对照组,miR-146a基因甲基化水平显著低于对照组(P＜0.05)。血浆miR-146a水平与miR-146a基因甲基化水平呈负相关(P＜0.05)。随疾病活动程度的增加,RA患者血浆miR-146a水平呈升高趋势,miR-146a基因甲基化水平呈下降趋势(P＜0.05)。血浆miR-146a水平与DAS28-ESR评分、ESR、C反应蛋白水平、关节肿胀计数、关节压痛计数、患者主观总体评估、医生总体评估、简化疾病活动指数呈正相关(P＜0.05);miR-146a基因甲基化水平与上述指标呈负相关(P＜0.05)。结论: 血浆miR-146a及基因甲基化状态与RA患者疾病活动程度有关,有望作为诊断和控制RA疾病活动的潜在标志物。

Objective: To investigate the relationship between the plasma microRNA(miRNA)-146a expression, gene hypermethylation and the disease activity in patients with rheumatoid arthritis(RA). Methods: From March 2019 to April 2020, 122 RA patients were recruited into RA group in the rheumatology department of our hospital. The disease activity was measured using the 28-joint disease activity score obtained on the basis of erythrocyte sedimentation rate(ESR) (DAS28-ESR). During the same period, another 141 healthy volunteers were included as control group. The plasma miR-146a level was detected by real-time fluorescence quantitative PCR,and the methylation status was analyzed by real-time fluorescence quantitative methylation specific PCR(qMSP). Results: The plasma miR-146a level in the RA group was significantly higher than that in the control group, and the methylation level of miR-146a gene was significantly lower than that in the control group(P＜0.05). Plasma miR-146a level was negatively correlated with miR-146a gene methylation level(P＜0.05). With the increase of disease activity, the plasma level of miR-146a increased and the methylation level of miR-146a gene decreased(P＜0.05). The plasma miR-146a level was positively correlated with DAS28-ESR, ESR, C-reactive protein, joint swelling count, joint tenderness count, patients' subjective global assessment, physician's global assessment and simplified disease activity index(P＜0.05). The methylation level of miR-146a gene was negatively correlated with the above indexes(P＜0.05). Conclusion: Plasma miR-146a and gene methylation status are related to the degree of disease activity in RA patients and may be potential markers for the diagnosis and control of RA disease activity.

参考文献：

[1] 段毅,易谭勇,朱乐全,等.LncRNA MEG3调控miR-328影响类风湿性关节炎滑膜细胞增殖、凋亡和炎性反应[J].中国组织化学与细胞化学杂志,2021,30(2):136-145.
[2] 郭淑芳,姜婷婷.下调miR-217抑制类风湿性关节炎患者外周血单个核细胞炎症反应的实验研究[J].中国免疫学杂志,2020,36(8):933-938.
[3] PAYET M,DARGAI F,GASQUE P,et al.Epigenetic regulation(including micro-RNAs,DNA methylation and histone modifications) of rheumatoid arthritis:a systematic review[J].Int J Mol Sci,2021,22(22):12170-12187.
[4] 朱嘉豪,陈婷,习欠云.miR-146a参与不同疾病的研究进展[J].中国生物工程杂志,2021,41(9):64-70.
[5] 胡钰镔,陈德丽,施月娟,等.外周血单个核细胞miR-146a和微管相关蛋白1轻链3及红细胞沉降率与类风湿关节炎疾病活动的关系[J].中华实用诊断与治疗杂志,2022,36(1):68-71.
[6] BAE S C,LEE Y H.MiR-146a levels in rheumatoid arthritis and their correlation with disease activity:a meta-analysis[J].Int J Rheum Dis,2018,21(7):1335-1342.
[7] ZHAO J,CHEN B,PENG X,et al.Quercetin suppresses migration and invasion by targeting miR-146a/GATA6 axis in fibroblast-like synoviocytes of rheumatoid arthritis[J].Immunopharmacol Immunotoxicol,2020,42(3):221-227.
[8] PAPATHANASIOU I,TRACHANA V,MOURMOURA E,et al.DNA methylation regulates miR-140-5p and miR-146a expression in osteoarthritis[J].Life Sci,2019,228:274-284.
[9] 魏亭亭,秦苇,冯伟伟,等.类风湿关节炎患者疲劳程度与疾病活动度的关系[J].浙江医学,2021,43(16):1781-1784.
[10] KOLARZ B,CIESLA M,DRYGLEWSKA M,et al.Hypermethylation of the miR-155 gene in the whole blood and decreased plasma level of miR-155 in rheumatoid arthritis[J].PLoS One,2020,15(6):e0233897.
[11] FUNES S C,FERNANDEZ-FIERRO A,REBOLLEDO-ZELADA D,et al.Contribution of dysregulated DNA methylation to autoimmunity[J].Int J Mol Sci,2021,22(21):11892-11911.
[12] IACONA J R,MONTELEONE N J,LUTZ C S.miR-146a suppresses 5-lipoxygenase activating protein(FLAP) expression and Leukotriene B4 production in lung cancer cells[J].Oncotarget,2018,9(42):26751-26769.
[13] BAGHERI-HOSSEINABADI Z,MIRZAEI M R,HAJIZADEH M R,et al.Plasma microRNAs(miR-146a,miR-103a,and miR-155) as potential biomarkers for rheumatoid arthritis(RA) and disease activity in Iranian patients[J].Mediterr J Rheumatol,2021,32(4):324-330.
[14] KMIOLEK T,RZESZOTARSKA E,WAJDA A,et al.The interplay between transcriptional factors and microRNAs as an important factor for Th17/Treg balance in RA patients[J].Int J Mol Sci,2020,21(19):7169-7186.
[15] ERFAN R,SHAKER O G,KHALIL M A F,et al.Long non-coding RNA PVT1 and its target miRNA-146a as potential prognostic biomarkers in rheumatoid arthritis patients[J].Life(Basel),2021,11(12):1382-1395.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录