In silico analysis of serum miRNA profiles in seronegative and seropositive rheumatoid arthritis patients by small RNA sequencing

Abstract

Rheumatoid arthritis (RA) is a refractory autoimmune disease, affecting about 1% of the world’s population. RA is divided into seronegative RA and seropositive RA. However, biomarkers for discriminating between seronegative and seropositive RA have not been reported. In this study, we profiled serum miRNAs in seronegative RA patients (N-RA), seropositive RA patients (P-RA) and healthy controls (HC) by small RNA sequencing. Results indicated that compared with HC group, there were one up-regulated and four downregulated miRNAs in N-RA group (fold change ≥ 2 and P value < 0.05); compared with P-RA group, there were two up-regulated and four downregulated miRNAs in N-RA group; compared with HC group, there were three up-regulated and four downregulated miRNAs in P-RA group. Among them, the level of hsa-miR-362-5p in N-RA group was up-regulated compared with that in HC group and P-RA group, and the level of hsa-miR-6855-5p and hsa-miR-187-3p in P-RA group was upregulated compared with that in N-RA group and HC group. Validation by qPCR confirmed that serum hsa-miR-362-5p level was elevated in N-RA group. Subsequently, by analyzing the target genes using RNAhybrid, PITA, Miranda and TargetScan and functions of differential miRNAs utilizing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), we found that the target genes and molecular pathways regulated by miRNAs in seronegative RA and seropositive RA were roughly the same, and miRNAs in these two diseases may participate in the occurrence and development of diseases by regulating the immune system. In conclusion, this study revealed the profiles of serum miRNAs in seronegative and seropositive RA patients for the first time, providing potential biomarkers and targets for the diagnosis and treatment of seronegative and seropositive RA.

Clinical Phenotypes, Serological Biomarkers, and Synovial Features Defining Seropositive and Seronegative Rheumatoid Arthritis: A Literature Review

“…Multiple studies have reported miRNAs involved in pro-inflammatory signalling pathways in RA patients leading to increased production of inflammatory cytokines [148][149][150][151]. A recent study by He et al compared different miRNAs between seropositive RA, seronegative RA, and healthy controls [152]. Interestingly, differences between seropositive and seronegative patients were found, with hsa-miR-362-5p more upregulated in the seronegative RA group, and hsa-miR-187-3P and hsa-miR-6855-5p being upregulated in the seropositive group.…”

When Autoantibodies Are Missing: The Challenge of Seronegative Rheumatoid Arthritis

“…In this regard, it was recently reported that the miRNAs has-miR-362-5p and has-miR-708-3p were upregulated in SNRA but not in SPRA. Other miRNAs were found to be downregulated differently in the two forms of RA, including the mRNAs expressed exclusively in SPRA and others common to both forms [27,28]. Table 1 summarizes the different genetic backgrounds and miRNA expressions between SNRA and SPRA.…”

“…Table 1 summarizes the different genetic backgrounds and miRNA expressions between SNRA and SPRA. SNP CLYBL High No [26] has-miR-362-5p High Low [27] has-miR-708-3p High Low [28] has-miR-24 High High [30] has-miR-125a High High [30] has-miR-22 Low High [30] has-miR-361-5p Low High [30] has-miR-233-3p Low High [30] SNRA = seronegative rheumatoid arthritis; SPRA = seropositive rheumatoid arthritis; miRNA = microRNA; SNP = single-nucleotide polymorphism.…”