Department of Biomolecular Chemistry, Institute for Molecules and Materials and Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.
Department of Rheumatology, Radboud University Nijmegen, Nijmegen, the Netherlands.
Clin Exp Immunol. 2018 Sep;193(3):376-385. doi: 10.1111/cei.13156.
Small non-coding RNAs have emerged as possible biomarkers for various diseases including autoimmune diseases. A number of studies have demonstrated that the expression of specific microRNAs (miRNAs) is dysregulated in rheumatoid arthritis (RA). So far, all studies on miRNAs in RA patients have been performed using either microarray or reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses. Compared to RT-qPCR and microarray analyses, next-generation sequencing (NGS) allows the genome-wide analysis of small RNAs and the differentiation between miRNAs that differ by a single nucleotide. The application of NGS to the analysis of small RNAs circulating in sera of RA patients has not been reported. This study provides a global overview of the circulating small RNAs in the sera of RA patients and healthy subjects and identifies differences between these groups using NGS. Several classes of small RNAs, including hY RNA-derived fragments, tRNA-derived fragments and miRNAs, were determined. Differentially expressed individual small RNAs were verified by RT-qPCR. The levels of two miRNAs, miR-223-3p and miR-16-5p, were significantly lower in the sera from early RA patients than in those from established RA patients and healthy controls. In contrast, the serum level of miR-16-5p was higher in patients with established RA than in healthy control samples. These miRNAs may not only serve as biomarkers, but may also shed more light on the pathophysiology of RA.
小非编码 RNA 已成为各种疾病（包括自身免疫性疾病）的潜在生物标志物。许多研究表明，类风湿关节炎（RA）患者的特定 microRNAs（miRNAs）表达失调。到目前为止，所有关于 RA 患者 miRNAs 的研究都是使用微阵列或逆转录定量聚合酶链反应（RT-qPCR）分析进行的。与 RT-qPCR 和微阵列分析相比，下一代测序（NGS）允许对小 RNA 进行全基因组分析，并区分仅相差一个核苷酸的 miRNAs。NGS 应用于 RA 患者血清中小 RNA 的分析尚未见报道。本研究使用 NGS 对 RA 患者和健康受试者血清中的循环小 RNA 进行了全面分析，并确定了两组之间的差异。确定了包括 hY RNA 衍生片段、tRNA 衍生片段和 miRNAs 在内的几类小 RNA。通过 RT-qPCR 验证了差异表达的个别小 RNA。与健康对照组相比，早期 RA 患者血清中的两种 miRNA（miR-223-3p 和 miR-16-5p）水平明显较低，而 established RA 患者血清中的 miR-16-5p 水平较高。这些 miRNA 不仅可以作为生物标志物，而且可能更深入地了解 RA 的病理生理学。
