Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China.
The Second Hospital of Dalian Medical University, DaLian, China.
J Clin Lab Anal. 2022 Jun;36(6):e24451. doi: 10.1002/jcla.24451. Epub 2022 May 6.
To identify differentially expressed lncRNA, miRNA, and mRNA during the pathogenesis of gout, explore the ceRNA network regulatory mechanism of gout, and seek potential therapeutic targets.
First, gout-related chips were retrieved by GEO database. Then, the analysis of differentially expressed lncRNAs and mRNAs was conducted by R language and other software. Besides, miRNA and its regulated mRNA were predicted based on public databases, the intersection of differentially expressed mRNA and predicated mRNA was taken, and the lncRNA-miRNA-mRNA regulatory relationships were obtained to construct the ceRNA regulatory network. Subsequently, hub genes were screened by the STRING database and Cytoscape software. Then the DAVID database was used to illustrate the gene functions and related pathways of hub genes and to mine key ceRNA networks.
Three hundred and eighty-eight lncRNAs and 758 mRNAs were identified with significant differential expression in gout patient, which regulates hub genes in the ceRNA network, such as JUN, FOS, PTGS2, NR4A2, and TNFAIP3. In the ceRNA network, lncRNA competes with mRNA for miRNA, thus affecting the IL-17 signaling pathway, TNF signaling pathway, Oxytocin signaling pathway, and NF-κB signaling pathway through regulating the cell's response to chemical stress. The research indicates that five miRNAs (miR-429, miR-137, miR-139-5p, miR-217, miR-23b-3p) and five lncRNAs (SNHG1, FAM182A, SPAG5-AS1, HNF1A-AS1, UCA1) play an important role in the formation and development of gout.
The interaction in the ceRNA network can affect the formation and development of gout by regulating the body's inflammatory response as well as proliferation, differentiation, and apoptosis of chondrocytes and osteoclasts. The identification of potential therapeutic targets and signaling pathways through ceRNA network can provide a reference for further research on the pathogenesis of gout.
鉴定痛风发病过程中的差异表达长链非编码 RNA（lncRNA）、微小 RNA（miRNA）和信使 RNA（mRNA），探讨痛风的 ceRNA 网络调控机制，寻求潜在的治疗靶点。
首先，通过 GEO 数据库检索与痛风相关的芯片。然后，使用 R 语言和其他软件对差异表达的 lncRNA 和 mRNA 进行分析。此外，基于公共数据库预测 miRNA 及其调控的 mRNA，取差异表达 mRNA 和预测 mRNA 的交集，构建 lncRNA-miRNA-mRNA 调控关系，构建 ceRNA 调控网络。然后，通过 STRING 数据库和 Cytoscape 软件筛选枢纽基因。然后使用 DAVID 数据库阐明枢纽基因的基因功能和相关通路，并挖掘关键 ceRNA 网络。
在痛风患者中发现 388 个 lncRNA 和 758 个 mRNA 存在显著差异表达，这些差异表达的 lncRNA 调控 ceRNA 网络中的枢纽基因，如 JUN、FOS、PTGS2、NR4A2 和 TNFAIP3。在 ceRNA 网络中，lncRNA 与 mRNA 竞争 miRNA，从而通过调节细胞对化学应激的反应，影响 IL-17 信号通路、TNF 信号通路、催产素信号通路和 NF-κB 信号通路。研究表明，五种 miRNA（miR-429、miR-137、miR-139-5p、miR-217、miR-23b-3p）和五种 lncRNA（SNHG1、FAM182A、SPAG5-AS1、HNF1A-AS1、UCA1）在痛风的形成和发展中起重要作用。
ceRNA 网络的相互作用可以通过调节机体的炎症反应以及软骨细胞和破骨细胞的增殖、分化和凋亡来影响痛风的形成和发展。通过 ceRNA 网络鉴定潜在的治疗靶点和信号通路，可为进一步研究痛风的发病机制提供参考。
