Beijing International Science and Technology Cooperation Base of Antivirus Drug, Faculty of Environment and Life, Beijing University of Technology, Beijing, China.
Department of Clinical Laboratory, China-Japan Friendship Hospital, Beijing, China.
Comb Chem High Throughput Screen. 2024;27(18):2741-2752. doi: 10.2174/0113862073262471231011043339.
Gout is a common inflammatory arthritis, which is mainly caused by the deposition of monosodium urate (MSU) in tissues. Transcriptomics was used to explore the pathogenesis and treatment of gout in our work.
The objective of the study was to analyze and validate potential therapeutic targets and biomarkers in THP-1 cells that were exposed to MSU.
THP-1 cells were exposed to MSU. The inflammatory effect was characterized, and RNA-Seq analysis was then carried out. The differential genes obtained by RNA-Seq were analyzed with gene expression omnibus (GEO) series 160170 (GSE160170) gout-related clinical samples in the GEO database and gout-related genes in the GeneCards database. From the three analysis approaches, the genes with significant differences were verified by the differential genes' transcription levels. The interaction relationship of long non-coding RNA (lncRNA) was proposed by ceRNA network analysis.
MSU significantly promoted the release of IL-1β and IL-18 in THP-1 cells, which aggravated their inflammatory effect. Through RNA-Seq, 698 differential genes were obtained, including 606 differential mRNA and 92 differential `LncRNA. Cross-analysis of the RNA-Seq differential genes, the GSE160170 differential genes, and the gout-related genes in GeneCards revealed a total of 17 genes coexisting in the tripartite data. Furthermore, seven differential genes-C-X-C motif chemokine ligand 8 (CXCL8), C-X-C motif chemokine ligand 2 (CXCL2), tumor necrosis factor (TNF), C-C motif chemokine ligand 3 (CCL3), suppressor of cytokine signaling 3 (SOCS3), oncostatin M (OSM), and MIR22 host gene (MIR22HG)-were verified as key genes that analyzed the weight of genes in pathways, the enrichment of inflammationrelated pathways, and protein-protein interaction (PPI) nodes combined with the expression of genes in RNA-Seq and GSE160170. It is suggested that MIR22HG may regulate OSM and SOCS3 through microRNA 4271 (miR-4271), OSM, and SOCS3m; CCL3 through microRNA 149-3p (miR-149-3p); and CXCL2 through microRNA 4652-3p (miR-4652-3p).
The potential of CXCL8, CXCL2, TNF, CCL3, SOCS3, and OSM as gout biomarkers and MIR22HG as a therapeutic target for gout are proposed, which provide new insights into the mechanisms of gout biomarkers and therapeutic methods.
痛风是一种常见的炎性关节炎，主要由单钠尿酸盐（MSU）在组织中的沉积引起。在本研究中，我们采用转录组学方法探讨痛风的发病机制和治疗方法。
分析并验证 THP-1 细胞中暴露于 MSU 时的潜在治疗靶点和生物标志物。
将 THP-1 细胞暴露于 MSU 中，观察其炎症效应，并进行 RNA-Seq 分析。利用基因表达综合数据库（GEO）系列 GSE160170（GSE160170）中的 GEO 数据库中痛风相关的临床样本和 GeneCards 数据库中的痛风相关基因对 RNA-Seq 获得的差异基因进行分析。通过三种分析方法，验证差异基因转录水平的差异基因。通过 ceRNA 网络分析提出长链非编码 RNA（lncRNA）的相互作用关系。
MSU 可显著促进 THP-1 细胞中白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）的释放，加重其炎症效应。通过 RNA-Seq 获得 698 个差异基因，包括 606 个差异 mRNA 和 92 个差异 lncRNA。对 RNA-Seq 差异基因、GSE160170 差异基因和 GeneCards 中的痛风相关基因进行交叉分析，发现共有 17 个基因在三方数据中共存。进一步验证了 7 个差异基因-C-X-C 基序趋化因子配体 8（CXCL8）、C-X-C 基序趋化因子配体 2（CXCL2）、肿瘤坏死因子（TNF）、C-C 基序趋化因子配体 3（CCL3）、细胞因子信号转导抑制因子 3（SOCS3）、抑瘤素 M（OSM）和微 RNA22 宿主基因（MIR22HG），是分析通路中基因权重、炎症相关通路富集以及与 RNA-Seq 和 GSE160170 中基因表达相结合的蛋白-蛋白相互作用（PPI）节点的关键基因。提示 MIR22HG 可能通过 microRNA4271（miR-4271）、OSM 和 SOCS3m 调节 OSM 和 SOCS3；CCL3 通过 microRNA149-3p（miR-149-3p）；CXCL2 通过 microRNA4652-3p（miR-4652-3p）。
提出 CXCL8、CXCL2、TNF、CCL3、SOCS3 和 OSM 作为痛风生物标志物，MIR22HG 作为痛风治疗靶点的潜力，为痛风生物标志物和治疗方法的机制提供了新的见解。
