Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Center, West China Hospital, Sichuan University, Chengdu, China.
Department of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
PLoS One. 2021 Feb 18;16(2):e0232918. doi: 10.1371/journal.pone.0232918. eCollection 2021.
To determine the expression profile and clinical significance of long non-coding RNAs (lncRNAs) in peripheral blood mononuclear cells (PBMCs) of patients with primary gout and healthy control subjects. Human lncRNA microarrays were used to identify the differentially expressed lncRNAs and mRNAs in primary gout patients (n = 6) and healthy control subjects (n = 6). Bioinformatics analyses were performed to predict the roles of differently expressed lncRNAs and mRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression levels of 8 lnRNAs in 64 primary gout patients and 32 healthy control subjects. Spearman's correlation was used to analyze the correlation between these eight lncRNAs and the laboratory values of gout patients. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of the lncRNAs identified in gout. The microarray analysis identified 1479 differentially expressed lncRNAs (879 more highly expressed and 600 more lowly expressed), 862 differentially expressed mRNAs (390 more highly expressed and 472 more lowly expressed) in primary gout (fold change > 2, P < 0.05), respectively. The bioinformatic analysis indicated that the differentially expressed lncRNAs regulated the abnormally expressed mRNAs, which were involved in the pathogenesis of gout through several different pathways. The expression levels of TCONS_00004393 and ENST00000566457 were significantly increased in the acute gout flare group than those in the intercritical gout group or healthy subjects (P<0.01). Moreover, inflammation indicators were positive correlated with TCONS_00004393 and ENST00000566457 expression levels. The areas under the ROC curve of ENST00000566457 and NR-026756 were 0.868 and 0.948, respectively. Our results provide novel insight into the mechanisms of primary gout, and reveal that TCONS_00004393 and ENST00000566457 might be as candidate targets for the treatment of gout flare; ENST00000566457 and NR-026756 could effectively discriminate between the gout and the healthy control groups.
为了确定原发性痛风患者外周血单个核细胞（PBMC）中长链非编码 RNA（lncRNA）的表达谱和临床意义。使用人类 lncRNA 微阵列鉴定原发性痛风患者（n=6）和健康对照者（n=6）中差异表达的 lncRNA 和 mRNA。进行生物信息学分析以预测差异表达的 lncRNA 和 mRNA 的作用。进行实时定量聚合酶链反应（qRT-PCR）以检测 64 例原发性痛风患者和 32 例健康对照组中 8 个 lncRNA 的表达水平。采用 Spearman 相关分析评估这 8 个 lncRNA 与痛风患者实验室值之间的相关性。构建受试者工作特征（ROC）曲线以评估在痛风中鉴定的 lncRNA 的诊断价值。微阵列分析鉴定出 1479 个差异表达的 lncRNA（879 个上调和 600 个下调），862 个差异表达的 mRNA（390 个上调和 472 个下调）在原发性痛风中（倍数变化>2，P<0.05）。生物信息学分析表明，差异表达的 lncRNA 调节异常表达的 mRNA，通过几种不同的途径参与痛风的发病机制。在急性痛风发作组中，TCONS_00004393 和 ENST00000566457 的表达水平明显高于间歇期痛风组或健康受试者（P<0.01）。此外，炎症指标与 TCONS_00004393 和 ENST00000566457 的表达水平呈正相关。ENST00000566457 和 NR-026756 的 ROC 曲线下面积分别为 0.868 和 0.948。我们的结果为原发性痛风的发病机制提供了新的见解，并表明 TCONS_00004393 和 ENST00000566457 可能是痛风发作的治疗靶点；ENST00000566457 和 NR-026756 可有效区分痛风组和健康对照组。
