Silva Isaura Isabelle Fonseca Gomes da, Nascimento Denise de Queiroga, Barbosa Alexandre Domingues, Souto Fabricio Oliveira, Maia Maria de Mascena Diniz, Crovella Sergio, Souza Paulo Roberto Eleuterio de, Sandrin-Garcia Paula
Universidade Federal de Pernambuco, Programa de Pós-Graduação em Genética e Biologia Molecular, Recife, PE, Brazil.
Instituto Keizo Asami, Recife, PE, Brazil.
Genet Mol Biol. 2024 Jul 26;47(2):e20230235. doi: 10.1590/1678-4685-GMB-2023-0235. eCollection 2024.
We predicted miRNAs with regulatory impact on NFKB1 and TRAF6 gene expression and selected the miR-194-5p, miR-124-3p, miR-9-5p, and miR-340-5p and their target genes for expression analyses on CD14+ monocytes from rheumatoid arthritis (RA) patients and healthy controls. Additionally, we evaluated the influence of genes and miRNA expression on RA patients' cytokine levels. No difference was observed in genes or miRNAs expression when compared to healthy controls and RA patients or clinical parameters. However, we found a significant difference between miR-194-5p and miR-9-5p levels (FC=-2.31; p=0.031; FC=-3.05;p=0.031, respectively) and non-prednisone users as compared to prednisone using patients. We conducted correlation analyses to identify the strength of the relationship between expression data and cytokine plasma levels. We observed a moderate positive correlation between miR-124-3p expression and IL-6 plasma levels (r=0.46; p=0.033). In addition, overexpression of miRNAs was concomitant to TRAF6 and NFKB1 genes as indicated by correlation analyses: TRAF6 and miR-194-5p (r=0.60;p<0.001) and miR-9-5p (r=0.63;p<0.001) and NFKB1 and miR-194-5p (r=0.72;p<0.001), miR-9-5p (r=0.72;p<0.001) and miR-340-5p (r=0.61;p<0.001). NFKB1 and TRAF6 genes and miRNAs monocyte expression do not appear to be related to RA but showed a significant difference in different groups of RA therapy. In addition, increased levels of miRNAs can be linked to concomitant overexpression of TRAF6 and NFKB1 in monocytes and act as its regulators.
我们预测了对NFKB1和TRAF6基因表达具有调控作用的微小RNA（miRNA），并选择了miR-194-5p、miR-124-3p、miR-9-5p和miR-340-5p及其靶基因，用于对类风湿性关节炎（RA）患者和健康对照者的CD14+单核细胞进行表达分析。此外，我们评估了基因和miRNA表达对RA患者细胞因子水平的影响。与健康对照者以及RA患者或临床参数相比，未观察到基因或miRNA表达存在差异。然而，我们发现，与使用泼尼松的患者相比，非泼尼松使用者的miR-194-5p和miR-9-5p水平存在显著差异（分别为FC=-2.31；p=0.031；FC=-3.05；p=0.031）。我们进行了相关性分析，以确定表达数据与细胞因子血浆水平之间关系的强度。我们观察到miR-124-3p表达与IL-6血浆水平之间存在中度正相关（r=0.46；p=0.033）。此外，相关性分析表明，miRNA的过表达与TRAF6和NFKB1基因同时出现：TRAF6与miR-194-5p（r=0.60；p<0.001）和miR-9-5p（r=0.63；p<0.001），以及NFKB1与miR-194-5p（r=0.72；p<0.001）、miR-9-5p（r=0.72；p<0.001）和miR-340-5p（r=0.61；p<0.001）。NFKB1和TRAF6基因以及miRNA在单核细胞中的表达似乎与RA无关，但在不同的RA治疗组中显示出显著差异。此外，miRNA水平的升高可能与单核细胞中TRAF6和NFKB1的同时过表达有关，并作为其调节因子发挥作用。
