Dai Fei, Zhang Quan-Bo, Tang Yi-Ping, He Yi-Xi, Yi Ting, Qing Yu-Feng
Research Center of Hyperuricemia and Gout, Affiliated Hospital of North Sichuan Medical College, North Sichuan Medical College, Nanchong, China.
Department of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, North Sichuan Medical College, Nanchong, China.
Front Genet. 2021 Oct 26;12:728091. doi: 10.3389/fgene.2021.728091. eCollection 2021.
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 ( = 5) and healthy controls (HC; = 3). Bioinformatics methods were used to analyze significantly different circRNAs (fold change >1.5, < 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, < 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; < 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.
环状RNA（circRNAs）是具有单链共价闭环结构的非编码RNA（ncRNAs），其异常表达可能参与多种人类疾病的发病机制。目前，关于痛风中circRNAs的了解有限。在这项病例对照研究中，使用人类circRNA微阵列来鉴定原发性痛风患者（n = 5）和健康对照（HC；n = 3）外周血单个核细胞（PBMCs）中差异表达的circRNAs。采用生物信息学方法分析差异显著的circRNAs（倍数变化>1.5，P<0.05）。此外，选择4个差异显著表达的circRNAs进行定量实时聚合酶链反应，以检测90例痛风患者和60例HC中的表达水平。随后，建立circRNA-miRNA-mRNA网络以预测感兴趣的circRNAs的功能。微阵列分析表明，痛风组中有238个circRNAs上调，41个circRNAs下调（倍数变化>1.5，P<0.05）。生物信息学分析表明，差异表达的circRNAs通过多种途径参与痛风的发病机制。此外，痛风组中hsa_circRNA_103657和hsa_circRNA_000241的表达水平显著高于HC组，且两者均与脂质代谢参数显著相关。此外，hsa_circRNA_103657的曲线下面积为0.801（95%置信区间（CI）：0.730 - 0.871；P<0.001）。我们的结果为原发性痛风的发病机制提供了新的见解。在痛风患者的PBMCs中鉴定出差异表达的circRNAs，这些差异circRNAs可能在痛风的发生和发展中起重要作用。
