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miR-155 基因在全血中的高甲基化和类风湿关节炎患者血浆中 miR-155 水平的降低。

Hypermethylation of the miR-155 gene in the whole blood and decreased plasma level of miR-155 in rheumatoid arthritis.

机构信息

College of Medical Sciences, University of Rzeszow, Rzeszow, Poland.

Department of Rheumatology and Connective Tissue Disease, Medical University of Lublin, Lublin, Poland.

出版信息

PLoS One. 2020 Jun 2;15(6):e0233897. doi: 10.1371/journal.pone.0233897. eCollection 2020.

DOI:10.1371/journal.pone.0233897
PMID:32484820
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7266293/
Abstract

OBJECTIVES

miR-155 plays a critical role in the inflammatory process and in diseases such as rheumatoid arthritis (RA). miR155 gene expression is regulated by its gene promoter region CpG island methylation. Previous studies have shown inconsistent changes in circulating levels of mir-155 in RA patients. The aims of our study were to evaluate miR-155 levels in plasma, to investigate its gene methylation level, and to correlate these levels with RA disease activity.

METHODS

One hundred and twenty-five patients with RA, and 30 age and sex-matched healthy controls (HC) were enrolled. Whole blood and plasma samples were collected and stored at -80°C until analysis. DAS28 score at the time of the blood draw was used to assess RA disease activity. The methylation status of miR-155 host gene was determined in whole blood by quantitative real-time methylation-specific PCR (qPCR). miR-155 expression levels were evaluated by quantitative reverse transcription PCR.

RESULTS

We found significantly lower circulating miR155 levels in RA patients compared to HC. Interestingly, the miR-155 gene methylation level was significantly higher in RA patients than in HC. miR-155 levels did not correlate with ACPA or RF positivity or disease activity.

CONCLUSIONS

We show here higher miR-155 methylation in whole blood and lower plasma miR155 expression in RA patients in comparison to HC. The evaluation of miR-155 host gene methylation status or miR155 plasma level might be a potentially useful marker in RA determination.

摘要

目的

miR-155 在炎症过程和类风湿关节炎 (RA) 等疾病中发挥着关键作用。miR155 基因表达受其基因启动子区域 CpG 岛甲基化的调控。先前的研究表明,RA 患者循环 miR-155 水平的变化不一致。本研究旨在评估血浆中 miR-155 的水平,研究其基因甲基化水平,并将这些水平与 RA 疾病活动相关联。

方法

共纳入 125 例 RA 患者和 30 名年龄和性别匹配的健康对照者(HC)。采集全血和血浆样本,储存在-80°C 直至分析。在采血时使用 DAS28 评分评估 RA 疾病活动度。通过定量实时甲基化特异性 PCR(qPCR)检测全血中 miR-155 宿主基因的甲基化状态。通过定量逆转录 PCR 评估 miR-155 表达水平。

结果

我们发现 RA 患者的循环 miR155 水平明显低于 HC。有趣的是,RA 患者的 miR-155 基因甲基化水平明显高于 HC。miR-155 水平与 ACPA 或 RF 阳性或疾病活动度无关。

结论

与 HC 相比,我们发现 RA 患者全血中 miR-155 甲基化水平升高,血浆中 miR155 表达水平降低。评估 miR-155 宿主基因甲基化状态或 miR155 血浆水平可能是 RA 诊断的潜在有用标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503d/7266293/4e0f7d206dc7/pone.0233897.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503d/7266293/49882b7cf287/pone.0233897.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503d/7266293/b8927600143e/pone.0233897.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503d/7266293/4e0f7d206dc7/pone.0233897.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503d/7266293/49882b7cf287/pone.0233897.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503d/7266293/b8927600143e/pone.0233897.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503d/7266293/4e0f7d206dc7/pone.0233897.g003.jpg

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