Identification of circular RNAs hsa_circ_0140271 in peripheral blood mononuclear cells as a novel diagnostic biomarker for female rheumatoid arthritis

Yufeng Chen,Bin Wang,Ning Jiang,Junlong Zhong,Xuegang Li,Shuping Zhong,Jie Shang,Huading Lu,Xianghe Xu,Biao Wu

doi:10.1186/s13018-021-02794-8

Abstract

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease, which commonly affects women. Accumulating evidence shows that differentially expressed circular RNAs (circRNAs) play crucial roles in the progress of RA. However, the roles of circRNAs in female RA remains unclear. This study explores potential role and diagnostic value of hsa_circ_0140271 from peripheral blood mononuclear cells (PBMC) in female RA.MethodsDifferential expression of circRNAs was determined by RNA-sequencing in PBMC from 4 healthy controls (HC) and 4 RA patients, and we further measured the level of hsa_circ_0140271 in a validation cohort consisting of 47 RA and 47 HC via RT-qPCR. Besides, correlation studies with clinical variables were also examined. What’s more, we performed bioinformatics analysis to predict the potential role of hsa_circ_0140271.ResultsPBMC expression of hsa_circ_0140271 of female RA was significantly higher than that of female HC, and it was positively correlated with antistreptolysin (ASO). Furthermore, the receiver operating characteristic (ROC) curve indicated that hsa_circ_0140271 could distinguish female RA from female HC and female patients with ankylosing spondylitis (AS) or osteoarthritis (OA). Besides, the combined diagnosis anti-cyclic citrullinated peptide (Anti-CCP) + hsa_circ_0140271 could improve diagnostic accuracy with an area under the curve (AUC) of 0.818 to compared with Anti-CCP. Furthermore, KEGG pathway enrichment analysis indicated hsa_circ_0140271 may act as microRNA sponge and participate in fatty acid metabolism pathways.ConclusionHsa_circ_0140271 was likely to be used as a promising diagnostic biomarker for female RA; it may act as microRNA sponge to regulate fatty acid metabolism pathways in RA.

Highlights

Rheumatoid arthritis (RA) is a chronic autoimmune disease, which commonly affects women
We used cluster screening to analyze the effect of gender against the background of female healthy samples and male rheumatoid arthritis samples (Fig. 1b, c)
When dividing female RA and female healthy controls according to the cutoff values of hsa_circ_0140271, the results showed that IL-6, IL-8 and TNF-α expression was higher in the hsa_circ_0140271 positive group (Fig. 4c–e), while there was no significant difference in the level of IL-1α, IL-1β and INF-γ between two groups (Fig. 4a, b, f )

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease, which commonly affects women. The roles of circRNAs in female RA remains unclear. Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation and erosive arthrosynovitis, with a prevalence of 0.5%–1% in the worldwide [1, 2]. RA is more prevalent among women, with some studies suggesting as high as 3:1 female-to-male ratio. Genes from the X-chromosome are closely associated with RA. Interleukin 1 receptor-associated kinase (IRAK1) from the X-chromosome has been reported to be related to female predominant in RA [6]. Researches on X-chromosomal genes might be a good way to elucidate the mechanism of female RA etiology

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