Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
Connect Tissue Res. 2021 Sep;62(5):531-541. doi: 10.1080/03008207.2020.1797709. Epub 2020 Aug 26.
Bioinformatics analysis was performed on gene expression profile microarray data to identify the key genes activated through the TNF-α/TNFR1 signaling pathway in intervertebral disc degeneration (IDD). The common differentially expressed genes (co-DEGs) were calculated in nucleus pulposus (NP) cells and annulus fibrosus (AF) cells under TNF-α treatment or TNFR1 knockdown, which reveals the potential mechanism of TNF-α involvement in IDD and may provide new therapeutic targets for IDD.
Differentially expressed genes (DEGs) in TNF-α-treated or TNFR1-knockdown NP cells and AF cells were identified. Further analysis of the gene ontology (GO), signaling pathways and interaction networks of the DEGs or co-DEGs were conducted using the Database for Annotation, Visualization and Integrated Discovery, STRING Database, and Cytoscape software. The relationship between genes and musculoskeletal diseases, including IDD, was assessed with the Comparative Toxicogenomics Database. The predicted microRNAs corresponding to the co-DEGs were also identified by microRNA Data Integration Portal.
In NP cells, the DEGs (|logFoldChange|>2, adj.P < 0.01) were identified including 48 DEGs by TNF-α treatment and 74 DEGs by TNFR1 knockdown; in AF cells, correspondingly, 105 DEGs were identified. The co-DEGs between NP cells and AF cells were calculated including CXCL8, ICAM1, BIRC3, RELB, NFKBIA, and TNFAIP3. They may be the hub genes that were significantly associated with both NP cells and AF cells through the TNF-α/TNFR1 signaling pathway. The co-DEGs and corresponding predicted miRNAs may be potential therapeutic targets for IDD.
CXCL8, ICAM1, BIRC3, RELB, NFKBIA, and TNFAIP3 may have a synergistic effect on TNF-α-induced IDD development. IDD: Intervertebral disc degeneration; NP: Nucleus pulposus; AF: Annulus fibrosus; co-DEG: Common differentially expressed gene; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; PPI: Protein-protein interaction.
通过对 TNF-α/TNFR1 信号通路中基因表达谱微阵列数据进行生物信息学分析，确定椎间盘退变（IDD）中通过 TNF-α/TNFR1 信号通路激活的关键基因。在 TNF-α 处理或 TNFR1 敲低的情况下，计算核髓核（NP）细胞和纤维环（AF）细胞中的共同差异表达基因（co-DEGs），揭示 TNF-α 参与 IDD 的潜在机制，并为 IDD 提供新的治疗靶点。
鉴定 TNF-α 处理或 TNFR1 敲低的 NP 细胞和 AF 细胞中的差异表达基因（DEGs）。使用数据库注释、可视化和综合发现、STRING 数据库和 Cytoscape 软件对 DEGs 或 co-DEGs 的基因本体（GO）、信号通路和相互作用网络进行进一步分析。使用比较毒理学基因组数据库评估基因与包括 IDD 在内的肌肉骨骼疾病之间的关系。通过 microRNA 数据综合门户识别 co-DEGs 对应的预测 microRNA。
在 NP 细胞中，通过 TNF-α 处理鉴定到 48 个 DEGs（|logFoldChange|>2，adj.P<0.01）和通过 TNFR1 敲低鉴定到 74 个 DEGs；在 AF 细胞中，相应地鉴定到 105 个 DEGs。计算 NP 细胞和 AF 细胞之间的共同差异表达基因，包括 CXCL8、ICAM1、BIRC3、RELB、NFKBIA 和 TNFAIP3。它们可能是通过 TNF-α/TNFR1 信号通路与 NP 细胞和 AF 细胞均显著相关的关键基因。共同差异表达基因和相应的预测 microRNA 可能是 IDD 的潜在治疗靶点。
CXCL8、ICAM1、BIRC3、RELB、NFKBIA 和 TNFAIP3 可能对 TNF-α 诱导的 IDD 发展具有协同作用。IDD：椎间盘退变；NP：核髓核；AF：纤维环；co-DEG：共同差异表达基因；GO：基因本体；KEGG：京都基因与基因组百科全书；PPI：蛋白质-蛋白质相互作用。
