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基于全基因组芯片分析鉴定早期类风湿关节炎潜在的 miRNA 生物标志物:一项初步研究。

Identification of putative miRNA biomarkers in early rheumatoid arthritis by genome-wide microarray profiling: A pilot study.

机构信息

Unidad de Investigación Biomédica de Zacatecas, IMSS, Zacatecas, México; Departamento de Inmunología, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México.

Unidad de Investigación Biomédica de Zacatecas, IMSS, Zacatecas, México; Cátedras-CONACyT-Unidad de Investigación Biomédica de Zacatecas-IMSS, Zacatecas, México.

出版信息

Gene. 2019 Dec 15;720:144081. doi: 10.1016/j.gene.2019.144081. Epub 2019 Aug 29.

Abstract

Despite the existing research, the etiology of rheumatoid arthritis (RA), an autoimmune disease remains poorly understood with early and accurate diagnosis difficult to achieve. MicroRNAs (miRNAs) play an important role in biological processes as modulators of transcription and translation. Previous studies have demonstrated a downregulation of several genes in early RA stages and in addition, miRNAs may serve as early biomarkers of subclinical changes in early RA. When comparing the four groups (ANOVA P < 0.01, fold change > 4), we found 253 differentially expressed miRNAs. Of these, 97 miRNAs were identified as overexpressed in early rheumatoid arthritis. The validation of miRNA microarray expression was performed in a set by RT-qPCR and showed strong agreement with microarray expression data. The putative targets of overexpressed microRNAs in early RA were significantly enriched in apoptosis, tolerance loss and Wnt pathways. Moreover, ROC analysis showed values of AUC 0.76 and P < 0.05 for miR 361-5p, identifying this miRNA as a potential biomarker of disease. We identified specific microRNAs associated with early rheumatoid arthritis and proposed them as early biomarkers of disease. Our results provide novel insight into immune disease physiopathology and describe unreported microRNAs in RA with potential for clinical use.

摘要

尽管已经有了相关研究,但类风湿关节炎(RA)这一自身免疫性疾病的病因仍未被充分了解,早期且准确的诊断也难以实现。MicroRNAs(miRNAs)作为转录和翻译的调节剂,在生物过程中发挥着重要作用。先前的研究表明,在早期 RA 阶段有几个基因的表达下调,此外,miRNAs 可能作为早期 RA 亚临床变化的早期生物标志物。在比较四组(ANOVA P<0.01,fold change>4)时,我们发现了 253 个差异表达的 miRNAs。其中,97 个 miRNAs 在早期类风湿关节炎中被鉴定为过度表达。通过 RT-qPCR 对 miRNA 微阵列表达进行了验证,结果与微阵列表达数据具有很强的一致性。早期 RA 中过度表达的 microRNAs 的假定靶基因在凋亡、耐受性丧失和 Wnt 途径中显著富集。此外,ROC 分析显示 miR 361-5p 的 AUC 值为 0.76,P<0.05,表明该 miRNA 是疾病的潜在生物标志物。我们确定了与早期类风湿关节炎相关的特定 microRNAs,并提出它们作为疾病的早期生物标志物。我们的研究结果为免疫性疾病的病理生理学提供了新的见解,并描述了 RA 中具有潜在临床应用价值的未报道的 microRNAs。

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