miRNAs and NFKB1 and TRAF6 target genes: The initial functional study in CD14+ monocytes in rheumatoid arthritis patients

• Published in: Genetics and molecular biology Vol. 47; no. 2; p. e20230235
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Brazil Sociedade Brasileira de Genética 01-01-2024
• Subjects: BIOCHEMISTRY & MOLECULAR BIOLOGY; GENETICS & HEREDITY; miRNA; NFKB1; TRAF6; miRNA; TRAF6; NFKB1
• ISSN: 1415-4757; 1678-4685; 1678-4685
• DOI: 10.1590/1678-4685-GMB-2023-0235

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.