Objective: Circular RNAs (circRNAs) are a significant class of molecules involved in a wide range of diverse biological functions that are abnormally expressed in many types of diseases. The present study aimed to determine the circRNAs specifically expressed in peripheral blood mononuclear cells (PBMCs) from rheumatoid arthritis (RA) patients to identify their possible molecular mechanisms. Methods: To identify the circRNAs specifically expressed in RA, we started by sequencing the of PBMCs circRNA and microRNAs (miRNAs) from a RA group (n = 3) and a control group (n = 3). We constructed a network of differentially expressed circRNAs and miRNAs. Then, we selected differentially expressed circRNAs in PBMCs from 10 RA patients relative to 10 age-and sex-matched controls using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Spearman's correlation test was used to evaluate the correlation of circRNAs with biochemical measurements. Results: A total of 165 circRNAs and 63 miRNAs were differently expressed between RA patients and healthy people according to RNA-seq, including 109 circRNAs that were significantly up-regulated and 56 circRNAs that were down-regulated among the RA patients. RT-qPCR validation demonstrated that the expression levels of hsa circ 0001200, hsa circ 0001566, hsa circ 0003972, and hsa circ 0008360 were consistent with the results from the sequencing analysis. Then, we found that there were significant correlations between the circRNAs and disease severity. Conclusion: Generally, these results suggest that expression of hsa circ 0001200, hsa circ 0001566, hsa circ 0003972, and hsa circ 0008360 in PBMCs from RA patients may serve as potential biomarkers for the diagnosis of RA, and these circRNAs may influence the occurrence and development of RA.
Long noncoding RNAs (lncRNAs) are >200‐bp molecules that do not generally code for proteins. Human lncRNAs have well‐characterized roles in gene expression regulation, particularly with regard to protein‐coding genes, and their dysregulation has been linked to disease. Here, we set out to investigate changes in the expression of lncRNAs related to apoptosis and autophagy in the peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA). In addition, we aimed to correlate lncRNA expression profiles with clinical indexes and self‐perception of patients (SPP). To this end, we employed RNA sequencing of lncRNAs in PBMCs from three patients with RA and three healthy controls. We used bioinformatics to screen several dysregulated lncRNAs related to apoptosis and autophagy. To validate key lncRNA candidates, we performed quantitative reverse transcriptase–PCR on 20 patients with RA and 20 healthy controls. We found the expression of seven lncRNAs (MAPKAPK5‐AS1, ENST00000619282, C5orf17, LINC01189, LINC01006, DSCR9 and MIR22HG) was significantly altered in PBMCs of patients with RA. Receiver operating characteristic curve analysis suggested that MIR22HG [area under the curve (AUC) = 0.846, P = 0.000], DSCR9 (AUC = 0.783, P = 0.005), LINC01189 (AUC = 0.677, P = 0.034), MAPKAPK5‐AS1 (AUC = 0.644, P = 0.025) and ENST00000619282 (AUC = 0.636, P = 0.043) are potential biomarkers of RA. Spearman's correlation analysis revealed selected lncRNAs correlated with clinical indexes and SPP. Therefore, we highlight that some lncRNAs related to apoptosis and autophagy may serve as potential biomarkers for diagnosis and monitoring of RA progression, which also correlate with several clinical indexes and SPP.
Objective: To explore the role of the Act1/NF-κB signaling pathway in the development of hypercoagulation states in patients with rheumatoid arthritis (RA).Methods: Peripheral blood samples were taken from 30 RA patients and 20 healthy volunteers, as controls. Ex vivo correlates of disease severity, such as C-reactive protein, erythrocyte sedimentation rate, anti-cyclic citrullinated peptide and rheumatoid factor, and immunological activation, such as interleukin (IL)-10, IL-17 and IL-6 were measured biochemically. Factors derived from the coagulation fibrinolytic system were also determined, such as the number of platelets, platelet activating factor, platelet activating factor-acetylhydrolase, D-dimer, thrombin time, prothrombin time, partial thromboplastin time, and fibrinogen levels. Furthermore, analysis of NF-κB signaling molecules Act1, p65, p50, IκBα and IκB kinase α (IKKα) was performed using semi-quantitative reverse transcription and western blotting.Results: Compared with the healthy control group, the levels of D-dimer, fibrinogen, and the number of platelets were significantly increased in the peripheral blood of RA patients, whereas partial thromboplastin time and thrombin time were decreased. IL-4, IL-10 and PAF-AH were significantly decreased in the serum of RA patients, while IL-6, IL-17, Act1, p50, p65, IκBα and PAF were significantly increased. Multiple regression analysis showed that coagulant and fibrinolytic indexes correlated significantly with cytokines, NF-κB, activity indexes and clinical symptoms. Conclusion:Hypercoagulation state was prevalent in patients with RA and was related to inflammatory factors, activity indexes and activation of NF-κB. The results suggested that abnormal activation of the NF-κB signaling pathway and an imbalance of pro-and anti-inflammatory cytokines was the result of a disturbance in the coagulation-fibrinolytic system.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.