State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
PeerJ. 2023 Jul 27;11:e15690. doi: 10.7717/peerj.15690. eCollection 2023.
Rheumatoid arthritis (RA) is a refractory autoimmune disease, affecting about 1% of the world's population. RA is divided into seronegative RA and seropositive RA. However, biomarkers for discriminating between seronegative and seropositive RA have not been reported. In this study, we profiled serum miRNAs in seronegative RA patients (N-RA), seropositive RA patients (P-RA) and healthy controls (HC) by small RNA sequencing. Results indicated that compared with HC group, there were one up-regulated and four downregulated miRNAs in N-RA group (fold change ≥ 2 and value < 0.05); compared with P-RA group, there were two up-regulated and four downregulated miRNAs in N-RA group; compared with HC group, there were three up-regulated and four downregulated miRNAs in P-RA group. Among them, the level of hsa-miR-362-5p in N-RA group was up-regulated compared with that in HC group and P-RA group, and the level of hsa-miR-6855-5p and hsa-miR-187-3p in P-RA group was upregulated compared with that in N-RA group and HC group. Validation by qPCR confirmed that serum hsa-miR-362-5p level was elevated in N-RA group. Subsequently, by analyzing the target genes using RNAhybrid, PITA, Miranda and TargetScan and functions of differential miRNAs utilizing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), we found that the target genes and molecular pathways regulated by miRNAs in seronegative RA and seropositive RA were roughly the same, and miRNAs in these two diseases may participate in the occurrence and development of diseases by regulating the immune system. In conclusion, this study revealed the profiles of serum miRNAs in seronegative and seropositive RA patients for the first time, providing potential biomarkers and targets for the diagnosis and treatment of seronegative and seropositive RA.
类风湿关节炎（RA）是一种难治性自身免疫性疾病，影响世界人口的 1%左右。RA 分为血清阴性 RA 和血清阳性 RA。然而，用于区分血清阴性和血清阳性 RA 的生物标志物尚未报道。在这项研究中，我们通过小 RNA 测序对血清阴性 RA 患者（N-RA）、血清阳性 RA 患者（P-RA）和健康对照（HC）进行了血清 miRNA 谱分析。结果表明，与 HC 组相比，N-RA 组有一个上调和四个下调的 miRNA（倍数变化≥2 和 P 值<0.05）；与 P-RA 组相比，N-RA 组有两个上调和四个下调的 miRNA；与 HC 组相比，P-RA 组有三个上调和四个下调的 miRNA。其中，N-RA 组的 hsa-miR-362-5p 水平与 HC 组和 P-RA 组相比上调，P-RA 组的 hsa-miR-6855-5p 和 hsa-miR-187-3p 水平与 N-RA 组和 HC 组相比上调。qPCR 验证证实 N-RA 组血清 hsa-miR-362-5p 水平升高。随后，通过分析 RNAhybrid、PITA、Miranda 和 TargetScan 的靶基因以及差异 miRNA 的基因本体论（GO）和京都基因与基因组百科全书（KEGG）功能，我们发现血清阴性 RA 和血清阳性 RA 中 miRNA 调节的靶基因和分子途径大致相同，这些疾病中的 miRNA 可能通过调节免疫系统参与疾病的发生和发展。总之，这项研究首次揭示了血清阴性和血清阳性 RA 患者血清 miRNA 的特征，为血清阴性和血清阳性 RA 的诊断和治疗提供了潜在的生物标志物和靶点。
