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痛风和动脉粥样硬化关键基因的鉴定及分子调控网络的构建

Identification of key genes in gout and atherosclerosis and construction of molecular regulatory networks.

作者信息

Qing Gong, Yuan Zujun

机构信息

Gastroenterology Department, The People's Hospital of Chongqing Liangping District, Chongqing, China.

出版信息

Front Cardiovasc Med. 2024 Nov 29;11:1471633. doi: 10.3389/fcvm.2024.1471633. eCollection 2024.

Abstract

BACKGROUND

Gout is a type of chronic inflammatory disease linked to the accumulation of monosodium urate crystals, leading to arthritis. Studies have shown that patients with gout are more likely to develop atherosclerosis, but the specific mechanisms involved remain unknown. The purpose of the research was to explore the key molecules and potential mechanisms between gout and atherosclerosis.

METHODS

Gene expression profiles for gout as well as atherosclerosis were obtained from the Gene Expression Omnibus (GEO) database, then differential analysis was utilized to identify common differentially expressed genes (DEGs) between the two diseases. The analysis of functional enrichment was conducted to investigate the biological processes that the DEGs might be involved in. The Cytoscape software was utilized to develop a protein-protein interaction (PPI) network as well as identify hub genes, while LASSO analysis was employed to select key genes. The TRRUST database was utilized to forecast transcription factors (TFs), and the miRTarBase database was utilized to forecast miRNAs.

RESULTS

Four key genes, CCL3, TNF, CCR2, and CCR5, were identified. The receiver operating characteristic (ROC) curves showed that the areas under ROC curve (AUC) for these four key genes in both gout and atherosclerosis were greater than 0.9. The analysis of functional enrichment revealed that the DEGs were primarily involved in "regulation of T-cell activation", "chemokine signaling pathway", and other biological processes. The TRRUST prediction results indicated that RELA and NFKB1 are common regulatory transcription factors for CCR2, CCR5, CCL3, and TNF. The miRTarBase prediction results showed that hsa-miR-203a-3p is a common regulatory miRNA for TNF and CCR5.

CONCLUSION

This study preliminarily explored the potential key molecules and mechanisms between gout and atherosclerosis. These findings provide new insights for further research into identifying potential biomarkers and clinical treatment strategies for these two diseases.

摘要

背景

痛风是一种与尿酸钠晶体积累相关的慢性炎症性疾病,可导致关节炎。研究表明,痛风患者更易发生动脉粥样硬化,但其具体机制尚不清楚。本研究旨在探讨痛风与动脉粥样硬化之间的关键分子和潜在机制。

方法

从基因表达综合数据库(GEO)获取痛风和动脉粥样硬化的基因表达谱,然后进行差异分析以鉴定两种疾病之间的共同差异表达基因(DEG)。进行功能富集分析以研究DEG可能参与的生物学过程。利用Cytoscape软件构建蛋白质-蛋白质相互作用(PPI)网络并鉴定枢纽基因,同时采用LASSO分析选择关键基因。利用TRRUST数据库预测转录因子(TF),利用miRTarBase数据库预测微小RNA(miRNA)。

结果

鉴定出四个关键基因,即CCL3、TNF、CCR2和CCR5。受试者工作特征(ROC)曲线显示,这四个关键基因在痛风和动脉粥样硬化中的ROC曲线下面积(AUC)均大于0.9。功能富集分析表明,DEG主要参与“T细胞活化调节”、“趋化因子信号通路”等生物学过程。TRRUST预测结果表明,RELA和NFKB1是CCR2、CCR5、CCL3和TNF的共同调节转录因子。miRTarBase预测结果显示,hsa-miR-203a-3p是TNF和CCR5的共同调节miRNA。

结论

本研究初步探讨了痛风与动脉粥样硬化之间潜在的关键分子和机制。这些发现为进一步研究这两种疾病的潜在生物标志物和临床治疗策略提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c339/11638179/2f72144f0688/fcvm-11-1471633-g001.jpg

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