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作为终末期骨关节炎的重要枢纽基因

, , and as Significant Hub Genes in End-Stage Osteoarthritis.

作者信息

Malakootian Mahshid, Gholipour Akram, Oveisee Maziar

机构信息

Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

Orthopedics Department, School of Medicine, Bam University of Medical Sciences, Bam, Iran.

出版信息

Iran J Public Health. 2023 Dec;52(12):2651-2662. doi: 10.18502/ijph.v52i12.14326.

Abstract

BACKGROUND

Osteoarthritis is one of the principal causes of chronic joint disease and may progressively engender disability in elderly individuals. The present study aimed to identify differentially expressed genes and associated signaling pathways in end-stage osteoarthritis.

METHODS

Differentially expressed messenger RNAs in the early and end stages of osteoarthritis were examined through gene expression omnibus 2R (GEO2R) in the GSE32317 dataset. Subsequently, gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) analyses were conducted. Furthermore, microRNAs targeting hub genes were investigated using the miRcode database. This study was conducted jointly at Bam University of Medical Sciences and Rajaie Cardiovascular, Medical and Research Center on October 2022.

RESULTS

Differentially expressed data demonstrated downregulation in 134 genes and upregulation in 189 genes in end-stage knee osteoarthritis. The results of the enrichment and PPI analyses determined 4 end-stage knee osteoarthritis-related hub genes: , and . The knee osteoarthritis-related key genes were involved in the Wnt signaling, B cell receptor signaling, calcium signaling, circadian entrainment, arginine and proline metabolism, axon guidance, and cytokine-cytokine receptor pathways. Additionally, the microRNAs targeting the 4 aforementioned genes were predicted.

CONCLUSION

The present study is the first to provide fresh insights into the potential therapeutic targets of key genes, namely , and differentially expressed in end-stage osteoarthritis and their relevant signaling pathways and interactive microRNAs.

摘要

背景

骨关节炎是慢性关节疾病的主要病因之一,可能会使老年人逐渐致残。本研究旨在确定终末期骨关节炎中差异表达的基因及相关信号通路。

方法

通过基因表达综合数据库2R(GEO2R)在GSE32317数据集中检测骨关节炎早期和终末期差异表达的信使核糖核酸。随后,进行基因本体(GO)富集分析、京都基因与基因组百科全书(KEGG)分析和蛋白质-蛋白质相互作用(PPI)分析。此外,使用miRcode数据库研究靶向枢纽基因的微小核糖核酸。本研究于2022年10月在巴姆医科大学和拉贾心血管医学与研究中心联合开展。

结果

差异表达数据显示,终末期膝骨关节炎中有134个基因下调,189个基因上调。富集分析和PPI分析结果确定了4个终末期膝骨关节炎相关枢纽基因: 、 、 、 。膝骨关节炎相关关键基因参与Wnt信号通路、B细胞受体信号通路、钙信号通路、昼夜节律调节、精氨酸和脯氨酸代谢、轴突导向以及细胞因子-细胞因子受体通路。此外,还预测了靶向上述4个基因的微小核糖核酸。

结论

本研究首次为终末期骨关节炎中差异表达的关键基因 、 、 及其相关信号通路和相互作用的微小核糖核酸的潜在治疗靶点提供了新见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f9e/10903304/be28238d544f/IJPH-52-2651-g001.jpg

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