利用加权基因共表达网络识别椎间盘退变的关键模块和生物标志物

IF 3.4 3区 医学 Q1 ORTHOPEDICS
JOR Spine Pub Date : 2024-10-18 DOI:10.1002/jsp2.70004
Daqian Zhou, Tao Liu, Yongliang Mei, Jiale Lv, Kang Cheng, Weiye Cai, Silong Gao, Daru Guo, Xianping Xie, Zongchao Liu
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引用次数: 0

摘要

背景 椎间盘退行性变(IVDD)是一种与年龄相关的骨科退行性疾病,以反复发作的下背痛为特征,其发病机制尚不完全清楚。本研究旨在确定 IVDD 及其病因的关键生物标志物。 方法 我们从基因表达总库(Gene Expression Omnibus,GEO)数据库中获取了 GSE56081、GSE124272 和 GSE153761 三份基因表达图谱,并使用 limma 快速差异分析法在去除批次效应后鉴定正常样本和 IVDD 样本之间的差异表达基因(DEGs)。我们应用加权基因共表达网络(WGCNA)确定了 GSE124272 中的关键模块基因,并将这些基因与 DEGs 相交。接着,我们构建了蛋白质-蛋白质相互作用网络(PPI),并使用 Cytoscape 确定了前 10 个枢纽基因。利用基因本体(GO)和京都基因和基因组百科全书(KEGG)数据库进行了功能富集分析。利用 Western Blot (WB) 和 qRT-PCR 验证了三个关键基因。此外,我们还预测了参与枢纽基因共调控的 miRNA,并分析了 GSE116726 中的 miRNA 微阵列数据,以确定 4 个差异表达的 miRNA。 结果 我们通过生物信息学分析确定了 10 个枢纽基因,基因功能富集分析表明这些基因主要富集在 TNF 信号通路等通路中。我们选择了JUNB、SOCS3和CEBPB作为中心基因,并使用WB和qRT-PCR证实了它们的表达。与对照组相比,这三个基因在IVDD模型组中都表达过高。此外,我们还利用 miRNet 预测发现了参与枢纽基因共调的四个 miRNA:mir-191-5p、mir-20a-5p、mir-155-5p 和 mir-124-3p。通过limma差异分析,我们发现mir-191-5p、mir-20a-5p和mir-155-5p在IVDD样本中都出现了下调和表达,但mir-124-3p没有明显变化。 结论 JUNB、SOCS3 和 CEBPB 是 IVDD 的关键基因,它们受特定 miRNAs 的调控,为早期诊断和治疗目标提供了潜在的生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Identifying critical modules and biomarkers of intervertebral disc degeneration by using weighted gene co-expression network

Identifying critical modules and biomarkers of intervertebral disc degeneration by using weighted gene co-expression network

Background

Intervertebral disc degeneration (IVDD) is an age-related orthopedic degenerative disease characterized by recurrent episodes of lower back pain, the pathogenesis of which is not fully understood. This study aimed to identify key biomarkers of IVDD and its causes.

Methods

We acquired three gene expression profiles from the Gene Expression Omnibus (GEO) database, GSE56081, GSE124272, and GSE153761, and used limma fast differential analysis to identify differentially expressed genes (DEGs) between normal and IVDD samples after removing batch effects. We applied weighted gene co-expression network (WGCNA) to identify the key modular genes in GSE124272 and intersected these with DEGs. Next, A protein–protein interaction network (PPI) was constructed, and Cytoscape was used to identify the Top 10 hub genes. Functional enrichment analyses were performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Three key genes were validated using Western Blot (WB) and qRT-PCR. Additionally, we predicted miRNAs involved in hub gene co-regulation and analyzed miRNA microarray data from GSE116726 to identify four differentially expressed miRNAs.

Results

We identified 10 hub genes using bioinformatics analysis, gene function enrichment analysis revealed that they were primarily enriched in pathways, such as the TNF signaling pathway. We chose JUNB, SOCS3, and CEBPB as hub genes and used WB and qRT-PCR to confirm their expression. All three genes were overexpressed in the IVDD model group compared to the control group. Furthermore, we identified four miRNAs involved in the co-regulation of the hub genes using miRNet prediction: mir-191-5p, mir-20a-5p, mir-155-5p, and mir-124-3p. Using limma difference analysis, we discovered that mir-191-5p, mir-20a-5p, and mir-155-5p were all down-regulated and expressed in IVDD samples, but mir-124-3p showed no significant change.

Conclusion

JUNB, SOCS3, and CEBPB were identified as key genes in IVDD, regulated by specific miRNAs, providing potential biomarkers for early diagnosis and therapeutic targets.

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来源期刊
JOR Spine
JOR Spine ORTHOPEDICS-
CiteScore
6.40
自引率
18.90%
发文量
42
审稿时长
10 weeks
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