Circulating serum miR-223-3p and miR-16-5p as possible biomarkers of early rheumatoid arthritis

Abstract

Small non-coding RNAs have emerged as possible biomarkers for various diseases including autoimmune diseases. A number of studies have demonstrated that the expression of specific microRNAs (miRNAs) is dysregulated in rheumatoid arthritis (RA). So far, all studies on miRNAs in RA patients have been performed using either microarray or reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses. Compared to RT-qPCR and microarray analyses, next-generation sequencing (NGS) allows the genome-wide analysis of small RNAs and the differentiation between miRNAs that differ by a single nucleotide. The application of NGS to the analysis of small RNAs circulating in sera of RA patients has not been reported. This study provides a global overview of the circulating small RNAs in the sera of RA patients and healthy subjects and identifies differences between these groups using NGS. Several classes of small RNAs, including hY RNA-derived fragments, tRNA-derived fragments and miRNAs, were determined. Differentially expressed individual small RNAs were verified by RT-qPCR. The levels of two miRNAs, miR-223-3p and miR-16-5p, were significantly lower in the sera from early RA patients than in those from established RA patients and healthy controls. In contrast, the serum level of miR-16-5p was higher in patients with established RA than in healthy control samples. These miRNAs may not only serve as biomarkers, but may also shed more light on the pathophysiology of RA.

The tRNA‐associated dysregulation in immune responses and immune diseases

“…89 Mechanism studies have found that endonuclease Dicer and angiogenin temporarily regulate the biogenesis of tRF5-AlaCGC, and this tRF could enhance IL-8 expression by activating p65. 91 Intriguingly, although the levels of tRFs in early RA were approximately the same as in healthy subjects, the proportion of reads mapped to tRNA in early RA was higher, which deserves our attention. 90 Dunaeva et al demonstrated that miR-223-3p and miR-16-5p were dysregulated in rheumatoid arthritis (RA) and could be used as biomarkers for this disease.…”

“…90 Dunaeva et al demonstrated that miR-223-3p and miR-16-5p were dysregulated in rheumatoid arthritis (RA) and could be used as biomarkers for this disease. 91 Intriguingly, although the levels of tRFs in early RA were approximately the same as in healthy subjects, the proportion of reads mapped to tRNA in early RA was higher, which deserves our attention.…”

Biological links in periodontitis and rheumatoid arthritis: Discovery via text‐mining PubMed abstracts

“…miRNA 26 are systemically elevated in RA, while hsa‐mir‐26b‐5p, in particular is implicated in autoimmune psoriasis . Hsa‐mir‐16‐5p regulates immune, apoptosis and epithelial barrier functions, and is an emerging biomarker of early disease and therapeutic response in RA . It is also upregulated in periodontitis .…”

“…73 Hsa-mir-16-5p regulates immune, apoptosis and epithelial barrier functions, and is an emerging biomarker of early disease and therapeutic response in RA. 74,75 It is also upregulated in periodontitis. 76 HMOX1 and SP1, the hub genes nodes in the gene-miRNA network both are involved in bone and immune regulation.…”

Inhibition of miR-16 enhances the sensitivity of fibroblast-like synovial cells to methotrexate by restraining MDR1/P-gp expressionviaNF-κB pathway

“…12 Previous studies illustrated that miR-16 were increased in the sera of established RA patients in comparison with early RA. 13,14 MiR-16 were shown to be overexpressed at the systemic level: in both the periphery and RA joints. 15 Upregulation of miR-16 is demonstrated to be involved in Th17/Treg cell imbalance in patients with RA.…”