鉴定miR-190a-5p和miR-26b-5p作为银屑病关节炎潜在的microRNA生物标志物

IF 2.8 Q2 RHEUMATOLOGY
Omar F Cruz-Correa, Darshini Ganatra, Ameth N Garrido, Rohan Machhar, Starlee Lively, Mohit Kapoor, Dafna D Gladman
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引用次数: 0

摘要

银屑病关节炎(Psoriatic arthritis, PsA)是一种慢性免疫介导的炎症性关节炎,在30%的银屑病患者中发生,导致发病率和死亡率增加,生活质量下降。MicroRNAs (miRNAs)调节基因表达,并与免疫介导疾病的发病机制有关。我们旨在鉴定可作为银屑病患者PsA发展的生物标志物的mirna。方法:采用新一代测序方法,对28例PsA患者、35例无关节炎皮肤银屑病(PsC)患者和28例健康对照者的血清样本进行miRNA表达水平评估。差异表达通过线性建模评估,经验贝叶斯适度校正测序批次,年龄,性别和牛皮癣持续时间。为了验证,我们在144名PsA患者和88名PsC患者的独立队列中,使用定制的NanoString探针板测量了>191基因的表达,这些基因预计将被失调的mirna靶向。利用pathDIP检测与差异表达基因靶点对应的特异性通路的富集情况。结果:在发现队列中,PsA患者miR-190a-5p与PsC患者相比显著下调(P< 0.05), PsA患者miR-190a-5p和miR-26b-5p与健康对照组相比均下调(P< 0.05)。在验证队列中,这两种mirna的26个基因靶点存在差异表达。这些基因在与骨形成和再生相关的信号通路中富集:Wnt和转化生长因子β。结论:miR-190a-5p和miR-26b-5p的血清表达水平可能作为PsA发展的生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of miR-190a-5p and miR-26b-5p as Potential microRNA Biomarkers for Psoriatic Arthritis.

Objective: Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory arthritis that develops in 30% of patients with psoriasis, leading to increased morbidity and mortality and reduced quality of life. MicroRNAs (miRNAs) modulate gene expression and have been associated with the pathogenesis of immune-mediated disorders. We aimed to identify miRNAs that can be used as biomarkers for the development of PsA in patients with psoriasis.

Methods: miRNA expression levels were assessed in serum samples from 28 patients with PsA, 35 patients with cutaneous psoriasis without arthritis (PsC), and 28 healthy controls through next-generation sequencing. Differential expression was assessed by linear modeling with empirical Bayes moderation corrected for sequencing batch, age, sex, and duration of psoriasis. For validation, we measured the expression of >191 genes predicted to be targeted by the dysregulated miRNAs using a custom NanoString probe panel in an independent cohort of 144 patients with PsA and 88 patients with PsC. The enrichment of specific pathways corresponding to the differentially expressed gene targets was examined using pathDIP.

Results: In the discovery cohort, the miRNA miR-190a-5p was significantly down-regulated in patients with PsA compared to those with PsC (P< 0.05), and both miR-190a-5p and miR-26b-5p were down-regulated in patients with PsA versus healthy controls (P < 0.05). In the validation cohort, 26 gene targets of both of these miRNAs were differentially expressed. These genes were enriched in signaling pathways associated with bone formation and regeneration: Wnt and transforming growth factor β.

Conclusion: Serum expression levels of miR-190a-5p and miR-26b-5p can potentially serve as biomarkers for PsA development.

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