Abstract

BackgroundCircular RNAs (circRNAs) represent a class of widespread and variety endogenous RNAs that may regulate gene expression. Thousands of mammalian circRNAs harbor miRNA response elements (MREs), suggesting a potential role as competitive endogenous RNAs (ceRNAs). Recent studies have demonstrated that ciRS-7 (circular CDR1 antisense), which acts as a powerful miR-7 sponge, contains more than 70 putative binding sites for miR-7 and may inhibit its target genes. The aim of this preliminary study was to investigate the expression of ciRS-7 in patients with rheumatoid arthritis (RA) as well as the correlation between ciRS-7 and the target genes of miR-7.MethodsEighteen patients with RA and 14 healthy controls were enrolled in the current study. The relative expression of ciRS-7, miR-7, miR-671 and mTOR in peripheral blood mononuclear cells (PBMCs) from these samples were detected by real-time PCR.ResultsWe found that ciRS-7 was significantly increased in RA patients and could potentially differentiate the RA patients from healthy controls. Additionally, the expression of mTOR, one of the miR-7 target genes, had positive and negative relationships with ciRS-7 and miR-7 expression, respectively. Notably, the relative expression of miR-671, which mediated the regulation of circular CDR1 antisense homeostasis, was significantly decreased in RA patients.ConlusionDownregulated miR-671 may influence the level of ciRS-7 in RA patients. Enhanced ciRS-7 could inhibit the function of miR-7 and further relieve the inhibitory effect of miR-7 on mTOR.

Highlights

  • Circular RNAs represent a class of widespread and variety endogenous RNAs that may regulate gene expression

  • The expression of ciRS-7 was increased in rheumatoid arthritis (RA) patients as described above, and we decided to examine the expression of ciRS-7

  • The relative expression of Mammalian target of rapamycin (mTOR) mRNA was detected in peripheral blood mononuclear cells (PBMCs) from RA patients

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Summary

Introduction

Circular RNAs (circRNAs) represent a class of widespread and variety endogenous RNAs that may regulate gene expression. Recent studies have demonstrated that ciRS-7 (circular CDR1 antisense), which acts as a powerful miR-7 sponge, contains more than 70 putative binding sites for miR-7 and may inhibit its target genes. The aim of this preliminary study was to investigate the expression of ciRS-7 in patients with rheumatoid arthritis (RA) as well as the correlation between ciRS-7 and the target genes of miR-7. PI3K/Akt/mTOR is one of the most important intracellular signaling pathways in mammalian cells [9, 10]. The role of the PI3K/AKT/mTOR pathway in promoting aggressive immune cell and synoviocyte proliferation and altered innate immunity in inflammatory arthritis was recently reviewed. One miR-7 target site was found in the mTOR 3’UTR, and miR-7 was reported to efficiently regulate the PI3K/Akt pathway by targeting PIK3CD, mTOR and p70S6K [18, 19]

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