Identification of the potential molecular targets for human intervertebral disc degeneration based on bioinformatic methods
Identification of the potential molecular targets for human intervertebral disc degeneration based on bioinformatic methods
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DOI：
10.3892/ijmm.2015.2389
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发表时间：
2015-12-01
影响因子：
5.4
通讯作者：
Wei, Haidong
中科院分区：
文献类型：
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作者：
He, Jiaxuan;Xue, Rongliang;Wei, Haidong
本研究旨在探索潜在的分子靶点，并进一步了解椎间盘退变（IDD）进展的机制。从Gene Expression Omnibus数据库下载GSE 19943、GSE 15227和GSE 34095的微阵列数据集。筛选GSE 34095中3例IDD标本与3例对照的差异表达基因（DEG）、GSE 19943中7例III级和3例IV级标本与5例II级标本的差异表达基因（DEG）、GSE 15227中3例变性标本与3例对照的差异表达miRNA。构建了III级和IV级特异性网络，并提取了等级特异性基因。分析网络特征，然后对GSE 34095中鉴定的等级特异性基因和DEG进行基因本体（GO）富集分析和途径富集分析。此外，使用Fisher精确检验分析miRNA-途径相互作用。肿瘤蛋白p53（TP 53）是III级特异性网络中的枢纽基因，泛素C（UBC）被鉴定为IV级特异性网络中的枢纽基因。六个显着特点，确定了特定等级的网络拓扑结构分析。年级特异性基因和DEG参与不同的GO术语和途径。差异表达的miRNAs参与了35条通路，其中6条通路被DEG显著富集，包括凋亡。本研究发现关键基因TP 53和UBC和miR-129- 5 p可能参与IDD的发病机制。因此，它们可能是IDD潜在的治疗靶点。
The present study aimed to explore potential molecular targets and gain further insights into the mechanism of intervertebral disc degeneration (IDD) progression. Microarray datasets of GSE19943, GSE15227 and GSE34095 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) in 3 IDD specimens compared with 3 controls in GSE34095, DEGs in 7 grade III and 3 grade IV samples compared with 5 grade II samples in GSE19943, and differentially expressed miRNAs in 3 degenerated samples compared with 3 controls in GSE15227 were screened. Grade III- and IV-specific networks were constructed and grade-specific genes were extracted. The network features were analyzed, followed by Gene Ontology (GO) enrichment analysis and pathway enrichment analysis of grade-specific genes and DEGs identified in GSE34095. Furthermore, miRNA-pathway interactions were analyzed using Fisher's exact test. Tumor protein p53 (TP53) was a hub gene in the grade III-specific network and ubiquitin C (UBC) was identified to be a hub gene in the grade IV-specific network. Six significant features were identified by grade-specific network topology analysis. Grade-specific genes and DEGs were involved in different GO terms and pathways. Differentially expressed miRNAs were identified to participate in 35 pathways, among which 6 pathways were significantly enriched by DEGs, including apoptosis. The present study identified that key genes (TP53 and UBC) and miR-129-5p may participate in the mechanism of IDD progression. Thus, they may be potential therapeutic targets for IDD.