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microRNAs 的表达改变可能预测类风湿关节炎患者的治疗反应。

Altered expression of microRNAs may predict therapeutic response in rheumatoid arthritis patients.

机构信息

Department of Immunology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Department of Immunology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran.

出版信息

Int Immunopharmacol. 2020 Jun;83:106404. doi: 10.1016/j.intimp.2020.106404. Epub 2020 Mar 18.

Abstract

BACKGROUND

Epigenetic alternations of microRNAs (miRNAs) can contribute to the pathogenesis and progression of rheumatoid arthritis (RA). This study aimed to measure the expression level of peripheral blood miRNAs, as well as their target mRNAs, in RA patients and healthy controls (HCs), and to evaluate the potential of miRNAs as promising non-invasive biomarkers of treatment response.

METHODS

The peripheral expression of miRNAs, including miR-146a, miR-146b, miR-150, miR-155, miR-125a-5p, miR-223, miR-26a, and miR-21, as well as their target mRNAs, was analyzed in 90 RA patients and 30 HCs via quantitative real-time polymerase chain reaction (RT-PCR) assay. We compared differences between the patients in terms of good response (GR; n = 55) and poor response (PR; n = 35) to the conventional therapeutic approach.

RESULTS

All miRNAs were significantly overexpressed in RA patients. The expression of miR-155, miR-150, miR-146a, miR-146b, miR-125a-5p, and miR-223 increased in both groups of RA patients, compared to HCs, and miR-26a and miR-21 were the only upregulated miRNAs in the GR group versus HCs. Among the upregulated miRNAs, miR-125a-5p expression significantly changed in GR and PR patients (P = 0.047). The ROC curve analysis indicated the potential involvement of miR-125a-5p in the pathogenesis of RA. We also observed the downregulated expression of GATA3, RORC, FOXP3, TBX21, STAT1, and TRAF6 in RA patients versus HCs.

CONCLUSION

Our findings indicated that different expression levels of miR-125a-5p in the GR and PR groups of patients may serve as a therapeutic response biomarker, which can be also used as a target for therapeutic interventions.

摘要

背景

微小 RNA(miRNA)的表观遗传学改变可能有助于类风湿关节炎(RA)的发病机制和进展。本研究旨在测量 RA 患者和健康对照者(HCs)外周血 miRNA 及其靶 mRNA 的表达水平,并评估 miRNA 作为有前途的治疗反应非侵入性生物标志物的潜力。

方法

通过实时定量聚合酶链反应(RT-PCR)检测 90 例 RA 患者和 30 例 HCs 外周血 miR-146a、miR-146b、miR-150、miR-155、miR-125a-5p、miR-223、miR-26a 和 miR-21 的表达及其靶 mRNA。我们比较了患者中对传统治疗方法反应良好(GR;n=55)和反应不良(PR;n=35)之间的差异。

结果

所有 miRNA 在 RA 患者中均显著过表达。与 HCs 相比,miR-155、miR-150、miR-146a、miR-146b、miR-125a-5p 和 miR-223 在两组 RA 患者中均表达增加,而 miR-26a 和 miR-21 是 GR 组与 HCs 相比唯一上调的 miRNA。在上调的 miRNA 中,miR-125a-5p 在 GR 和 PR 患者中的表达明显改变(P=0.047)。ROC 曲线分析表明 miR-125a-5p 可能参与了 RA 的发病机制。我们还观察到 RA 患者 GATA3、RORC、FOXP3、TBX21、STAT1 和 TRAF6 的表达下调。

结论

我们的研究结果表明,miR-125a-5p 在 GR 和 PR 患者中的不同表达水平可能作为治疗反应的生物标志物,也可以作为治疗干预的靶点。

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