Expression Profile and Potential Function of Circular RNAs in Peripheral Blood Mononuclear Cells in Male Patients With Primary Gout

Abstract

Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) with a single-stranded covalently closed-loop structure, and their abnormal expression may participate in the pathogenesis of various human diseases. Currently, knowledge of circRNAs in gout is limited. In this case-control study, human circRNA microarrays were used to identify differentially expressed circRNAs in peripheral blood mononuclear cells (PBMCs) from patients with primary gout (n = 5) and healthy controls (HC; n = 3). Bioinformatics methods were used to analyze significantly different circRNAs (fold change >1.5, p < 0.05). In addition, four significantly differentially expressed circRNAs were selected for quantitative real-time polymerase chain reaction to detect expression levels in 90 gout patients and 60 HC. Subsequently, circRNA-miRNA-mRNA network was established to predict the function of circRNAs of interest. Microarray analysis indicated that 238 circRNAs were upregulated and 41 circRNAs were down-regulated in the gout group (fold change >1.5, p < 0.05). Bioinformatics analysis showed that differentially expressed circRNAs were involved in the pathogenesis of gout via various pathways. Moreover, the expression levels of hsa_circRNA_103657 and hsa_circRNA_000241 were significantly higher in the gout group than those in the HC group, and both correlated significantly with lipid metabolism parameters. Furthermore, the area under the curve of hsa_circRNA_103657 was 0.801 (95% confidence interval (CI): 0.730–0.871; p < 0.001). Our results provide novel insights into the pathogenesis of primary gout. Differentially expressed circRNAs were identified in the PBMCs of gout patients, and these differential circRNAs may play important roles in the development and progression of gout.

Expression Profile of Pyroptosis-Related Genes and the Associated Regulatory Axis in Primary Gout Patients

“…Heatmap and Volcano plot analyses show these results (Figure1C-E. Differential identification of circRNA microarray data sets was consistent with our previous study(13), in which there were 279 DEcircRNAs, including 238 up-regulated and 41 down-regulated circRNAs.…”

“…NcRNAs, such as miRNA, LncRNA, cirRNA, are a class of RNAs that do not encode proteins and have crucial roles in human health and disease, including gout. [13][14][15] Current studies have shown that lncRNA and circRNA can act as a kind of ceRNA to regulate target gene expression by competing with related mRNAs to bind to the same miRNA through miRNA response elements. 16 Our team has long worked on ncRNA's role in gout.…”

“…The design and results of microarray data were based on previous reports. 13 , 14 Arraystar Human LncRNA Microarray V4.0 (Arraystar, Rockville, MD, USA) examined mRNA and lcnRNA expression in PBMCs of 6 primary gout patients and 6 HC matched by age and sex. Arraystar Human circRNA Array v2 (8 × 15K) (Arraystar, Rockville, MD, USA) examined circRNA expression in PBMCs from the peripheral blood of 5 age-and sex-matched patients with primary gout and 3 HC.…”

“…Transcriptome and microarray analysis have been widely used to identify new biomarkers for improved diagnosis and treatment of various diseases, including gout. [13][14][15] In addition, the competitive endogenous RNA (ceRNA) network can elucidate new mechanisms for promoting disease development in transcriptional regulatory networks. 16 Therefore, in this study, differential expression of mRNAs in peripheral blood mononuclear cells (PBMCs) between primary gout patients and healthy controls (HC) detected by microarray technology.…”

Hypomethylation of the opioid receptor delta 1 gene combined with high opioid receptor delta 1 protein levels indicates increased risk of gout

“…However, we did identify the differential expression of circular RNAs and long non‐coding RNAs, suggesting that they may be involved in the pathogenesis of gout through multiple pathways. 19 , 20 …”