Abstract
Long noncoding RNAs (lncRNAs) have recently emerged as important biological regulators, and the aberrant expression of lncRNAs has been reported in numerous diseases. However, the expression of lncRNAs in peripheral blood mononuclear cells (PBMCs) in rheumatoid arthritis (RA) has not been well documented. We applied a microarray analysis to profile the lncRNA and mRNA expression in 3 pairs of samples. Each sample was mixed with equivalent PBMCs from 9 female RA patients and 9 corresponding healthy controls, and the data were validated via qPCR using another cohort that comprised 36 RA patients and 24 healthy controls. A bioinformatic analysis was performed to investigate the potential functions of differentially expressed genes. Overall, 2,099 lncRNAs and 2,307 mRNAs were differentially expressed between the RA patients and healthy controls. The bioinformatic analysis indicated that the differentially expressed lncRNAs regulated the abnormally expressed mRNAs, which were involved in the pathogenesis of RA through several different pathways. The qPCR results showed that the expression levels of ENST00000456270 and NR_002838 were significantly increased in the RA patients, whereas the expression levels of NR_026812 and uc001zwf.1 were significantly decreased. Furthermore, the expression level of ENST00000456270 was strongly associated with the serum levels of IL-6 and TNF-a and the Simplified Disease Activity Index (SDAI) of the RA patients. Our data provided comprehensive evidence regarding the differential expression of lncRNAs in PBMCs of RA patients, which shed light on the understanding of the molecular mechanisms of lncRNAs in the pathogenesis of RA.
Highlights
Rheumatoid arthritis (RA) is the most common form of inflammatory and destructive arthritis and affects 0.5% to 1% of the general population worldwide
The results showed that the expression levels of NR_002838 and ENST00000456270 were strongly correlated with the Simplified Disease Activity Index (SDAI) (r = 0.5191, p = 0.0020 and r = 0.8347,p
Yang et al reported that Long noncoding RNAs (lncRNAs)-NR024118, which may be upregulated by Shikoninin, the CAIA mouse model of rheumatoid arthritis (RA), has the ability to inhibit the inflammatory response[26]. lncRNA-p21 has a low expression in RA, and methotrexate (MTX) can restore lncRNA-p21 levels to normal in vivo, which indicates that lncRNA-p21 may play an important role in the anti-inflammatory properties of MTX[27]
Summary
Rheumatoid arthritis (RA) is the most common form of inflammatory and destructive arthritis and affects 0.5% to 1% of the general population worldwide. Increasing evidence indicates that lncRNAs, as an versatile molecules that interact with RNA, DNA, or proteins to promote or restrain the expression of protein-coding genes, are involved in diverse biological processes, including cell proliferation, differentiation, apoptosis, and development[3,4,5]. In the field of immunology, various studies have indicated that lncRNAs are emerging as important regulators of inflammatory gene expression in innate immune system[6, 7], and play a crucial role in directing the development and apoptosis of diverse immune cells and controlling the dynamic transcriptional programs that are hallmarks of immune cells activation or differentiation in adaptive immune system[8,9,10,11]. We examined the lncRNA expression profile in female RA patients using microarray analysis to investigate the potential roles of lncRNAs in the pathogenesis of RA, assess the relationship between differentially expressed lncRNAs and clinical data, and explore novel biomarkers used in diagnosis, disease monitoring and prognosis
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