Dataset Information

Identification of key genes associated with the effect of osmotic stimuli on intervertebral discs using microarray analysis.

ABSTRACT: The present study aimed to explore the effect of osmotic stimuli on intervertebral discs (IVDs) using microarray analysis. Gene expression dataset GSE1648 was downloaded from the Gene Expression Omnibus database. There were 11 IVD cell samples in this dataset, which included 4 hyperosmotic stimuli samples, 3 hypoosmotic stimuli samples and 4 isosmotic stimuli samples. The differentially expressed genes (DEGs) in hyperosmotic or hypoosmotic IVD cells (designated DEGs-hyper or DEGs-hypo) were identified, compared with isosmotic cells, using the limma package of R software. The Database for Annotation, Visualization and Integrated Discovery was used to perform a Gene Ontology (GO) term enrichment analysis for the DEG sets. Protein-protein interaction (PPI) network and microRNA (miRNA) gene-regulatory network data for the DEG sets were obtained using the Human Protein Reference Database (HPRD) and the TargetScan database, respectively, and these networks were constructed and visualized using Cytoscape software. There was a total of 43 DEGs in DEGs-hyper and 9 in DEGs-hypo. Analysis of DEGs-hyper revealed that 41 GO terms were significantly enriched. In total, 376 pairs and 382 nodes were involved in the PPI network, and 1,314 miRNA-gene pairs and 422 nodes were contained in the miRNA-gene-regulated network. The results of the present study indicated that potential target genes (including NCOA3, SOS1, XPO1, ZBTB18, EFNB2 and SOBP) may be involved in the effect of osmotic stimuli on IVD, and the biological processes of apoptosis and cell death may be associated with the effect of high osmolality on IVD disease. The potential targets identified in the present study are more reliable than those identified by previous studies.

SUBMITTER: Ni G

PROVIDER: S-EPMC5592857 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Identification of key genes associated with the effect of osmotic stimuli on intervertebral discs using microarray analysis.

Ni Guangxiao G Liu Guobin G Yu Kunlun K

Oncology letters 20170724 4

The present study aimed to explore the effect of osmotic stimuli on intervertebral discs (IVDs) using microarray analysis. Gene expression dataset GSE1648 was downloaded from the Gene Expression Omnibus database. There were 11 IVD cell samples in this dataset, which included 4 hyperosmotic stimuli samples, 3 hypoosmotic stimuli samples and 4 isosmotic stimuli samples. The differentially expressed genes (DEGs) in hyperosmotic or hypoosmotic IVD cells (designated DEGs-hyper or DEGs-hypo) were iden ...[more]

PMID: 28943935

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Project description:Intervertebral disc (IVD) degeneration is a pathological process, which may lead to lower back pain. The present study aimed to investigate the pathogenesis of IVD degeneration. GSE42611 was downloaded from Gene Expression Omnibus, including 4 nucleus pulposus samples isolated from degenerated IVDs and 4 nucleus pulposus samples separated from normal IVDs. The differentially expressed genes (DEGs) between the degenerated and normal samples were screened using the limma package in R. Functional and pathway enrichment analyses were conducted separately for the upregulated and downregulated genes, using Database for Annotation, Visualization and Integrated Discovery software. In addition, protein‑protein interaction (PPI) networks were constructed using the Search Tool for the Retrieval of Interacting Genes database and Cytoscape software. Finally, module analyses were conducted for the PPI networks using the MCODE plug‑in in Cytoscape. A total of 558 DEGs were identified in the degenerated nucleus pulposus cells: 253 upregulated and 305 downregulated. Pathway enrichment analysis revealed that downregulated thrombospondin 1 (THBS1) was enriched in extracellular matrix‑receptor interaction. Interleukin (IL)‑6 in the PPI network for the upregulated genes and vascular endothelial growth factor A (VEGFA) in the PPI network for the downregulated genes had higher degrees. Additionally, four modules (µM1, µM2, µM3 and µM4) were identified from the PPI network for the upregulated genes. Four modules (dM1, dM2, dM3 and dM4) were identified from the PPI network for the downregulated genes. In the dM2 module, collagen genes and integrin subunit α4 (ITGA4) may interact with each other. Additionally, functional enrichment indicated that collagen genes were enriched in extracellular matrix organization. In conclusion, IL‑6, VEGFA, THBS1, ITGA4 and collagen genes may contribute to the progression of IVD degeneration. These results suggested that the manipulation of these genes and their products may have potential as a novel therapeutic strategy for the treatment of patients with IVD.

Project description:Background: Intervertebral disc degeneration impairs the quality of patients lives. Even though there has been development of many therapeutic strategies, most of them remain unsatisfactory due to the limited understanding of the mechanisms that underlie the intervertebral disc degeneration. Questions/purposes: This study is meant to identify the key modules and hub genes related to the annulus fibrosus in intervertebral disc degeneration (IDD) through: (1) constructing a weighted gene co-expression network; (2) identifying key modules and hub genes; (3) verifying the relationships of key modules and hub genes with IDD; and (4) confirming the expression pattern of hub genes in clinical samples. Methods: The Gene Expression Omnibus provided 24 sets of annulus fibrosus microarray data. Differentially expressed genes between the annulus fibrosus of degenerative and non-degenerative intervertebral disc samples have gone through the Gene Ontology (GO) and pathway analysis. The construction of a gene network and classification of genes into different modules were conducted through performing Weighted Gene Co-expression Network Analysis. The identification of modules and hub genes that were most related to intervertebral disc degeneration was proceeded. In order to verify the relationships of the module and hub genes with intervertebral disc degeneration, Ingenuity Pathway Analysis was operated. Clinical samples were adopted to help verify the hub gene expression profile. Results: One thousand one hundred ninety differentially expressed genes were identified. Terms and pathways associated with intervertebral disc degeneration were presented by GO and pathway analysis. The construction of a Weighted Gene Coexpression Network was completed and clustering differentially expressed genes into four modules was also achieved. The module with the lowest P-value and the highest absolute correlation coefficient was selected and its relationship with intervertebral disc degeneration was confirmed by Ingenuity Pathway Analysis. The identification of hub genes and the confirmation of their expression profile were also realized. Conclusions: This study generated a comprehensive overview of the gene networks underlying annulus fibrosus in intervertebral disc degeneration. Clinical Relevance: Modules and hub genes identified in this study are highly associated with intervertebral disc degeneration, and may serve as potential therapeutic targets for intervertebral disc degeneration.

Dataset Information

Identification of key genes associated with the effect of osmotic stimuli on intervertebral discs using microarray analysis.

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Identification of key genes associated with the effect of osmotic stimuli on intervertebral discs using microarray analysis.

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