Li Ming, Ma Kexun, Feng Zhe, Wang Jing, Zhou Xueping, Zhou Lingling
The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China.
Department of Rheumatology and Immunology, The Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.
Exp Ther Med. 2020 Jul;20(1):461-471. doi: 10.3892/etm.2020.8681. Epub 2020 Apr 23.
The human transcriptome is primarily composed of long non-coding RNAs (lncRNAs), which are key regulatory molecules of multiple biological processes. In the present study, the expression profiles of lncRNAs in the peripheral blood and CD4 T cells of patients with active rheumatoid arthritis (RA) were determined. Based on the expression profiles, 493 lncRNAs and 374 mRNAs were identified to be differentially expressed in the peripheral blood of active RA patients and healthy donors. Further verification of lncRNAs was performed using reverse transcription-quantitative (RT-q) PCR analysis of peripheral blood from 5 healthy donors and 5 patients with active RA and 14 additional differentially expressed genes were identified. CD4 T cells in peripheral blood from 12 patients with active RA and 8 healthy donors were isolated using magnetic beads and qPCR was used to assess differentially expressed lncRNAs. The results suggested that 7 lncRNAs were upregulated and 2 were downregulated. The results indicated that these 9 lncRNAs may be involved in the pathogenesis of RA. An increased ratio of Th17: T-regulatory (Treg) cells was also observed. It may be hypothesized that LncRNAs serve important roles in the differentiation of CD4 T cells. Receiver operating characteristic curve analysis suggested that these 9 lncRNAs are of potential clinical diagnostic value for RA. Pearson correlation analysis indicated that the correlation coefficient between Ensembl transcript (ENST)00000569543 and complement C4 was 0.623 (P<0.05), and that between ENST00000420096 and anti-cyclic citrullinated peptide antibody or disease activity evaluation score, the correlation coefficient was 0.662 and 0.605, respectively (P<0.05 for each). In conclusion, the results of the present study suggest a possible role of lncRNAs in the differentiation of CD4 T cells and the pathogenesis of RA, as well as the potential value as diagnostic biomarkers for active RA.
人类转录组主要由长链非编码RNA（lncRNA）组成，lncRNA是多种生物学过程的关键调控分子。在本研究中，测定了活动性类风湿关节炎（RA）患者外周血和CD4 T细胞中lncRNA的表达谱。基于该表达谱，鉴定出493个lncRNA和374个mRNA在活动性RA患者外周血和健康供体中差异表达。使用来自5名健康供体和5名活动性RA患者的外周血进行逆转录定量（RT-q）PCR分析对lncRNA进行进一步验证，并鉴定出另外14个差异表达基因。使用磁珠分离12名活动性RA患者和8名健康供体外周血中的CD4 T细胞，并使用qPCR评估差异表达的lncRNA。结果表明，7个lncRNA上调，2个lncRNA下调。结果表明，这9个lncRNA可能参与RA的发病机制。还观察到Th17与调节性T（Treg）细胞的比例增加。可以推测，lncRNA在CD4 T细胞分化中起重要作用。受试者工作特征曲线分析表明，这9个lncRNA对RA具有潜在的临床诊断价值。Pearson相关性分析表明，Ensembl转录本（ENST）00000569543与补体C4之间的相关系数为0.623（P<0.05），ENST00000420096与抗环瓜氨酸肽抗体或疾病活动评估评分之间的相关系数分别为0.662和0.605（均P<0.05）。总之，本研究结果表明lncRNA在CD4 T细胞分化和RA发病机制中可能起作用，以及作为活动性RA诊断生物标志物的潜在价值。
