利用生物信息学方法研究椎间盘退变发展过程中细胞凋亡相关的关键 miRNA 及其靶基因。
Investigation of key miRNAs and their target genes involved in cell apoptosis during intervertebral disc degeneration development using bioinformatics methods.
机构信息
Department of Orthopaedics, The General Hospital of Northern Theater Command, Shenyang, China.
The Second Clinical College of Graduate School, Dalian Medical University, Dalian, China.
出版信息
J Neurosurg Sci. 2022 Apr;66(2):125-132. doi: 10.23736/S0390-5616.20.04773-6. Epub 2020 Feb 4.
BACKGROUND
The aim of this study was to identify important miRNAs and their target genes involved in cell apoptosis in intervertebral disc degeneration (IDD) patients.
METHODS
The dataset, GSE63492, was obtained from the gene expression omnibus platform. After preprocessing, the differentially expressed miRNAs (DEMs) and their target genes were identified using the Limma package and miRWalk2.0 database, respectively. The clusterProfiler package in R was used to perform functional enrichment analysis of these target genes. Subsequently, protein-protein interaction (PPI) network and subnet clusters of the coregulated genes were conducted using the STRING database and MCODE, respectively. Further, the co-regulatory network of the key miRNAs and PPI networks were visualized using Cytoscape. Finally, cell apoptosis-related pathways and the genes enriched in these pathways were identified.
RESULTS
The genes targeted by the upregulated (hsa-miR-302c-5p, hsa-miR-631, hsa-let-7f-1-3p, hsa-miR-3675-3p, and hsa-miR-585-3p) and downregulated miRNAs (hsa-miR-185-5p, hsa-miR-486-5p, hsa-miR-4306, and hsa-miR-4674) were interrelated with cell apoptosis-related pathways. MAPK1 and MAPK3 were targeted by hsa-miR-185-5p, while GSK3B was targeted hsa-miR-4306, hsa-miR-486-5p, hsa-miR-185-5p, hsa-let-7f-1-3p, and hsa-miR-631. Besides, MAPK3 and VEGFA were regulated by hsa-miR-3675-3p and hsa-miR-631, respectively.
CONCLUSIONS
The expression of GSK3B may be coregulated by miR-4306, miR-185-5p, miR-486-5p, hsa-let-7f-1-3p, and miR-631 and may affect IDD development. Besides, miR-185-5p and miR-3675-3p may control nucleus pulposus (NP) cell apoptosis through the MAPK signaling pathway in IDD patients. VEGFA expression may be regulated by miR-631, and help maintain NP cell survival in IDD patients. Our findings may help guide further research into the role of miRNAs in IDD progression.
背景
本研究旨在鉴定参与椎间盘退变（IDD）患者细胞凋亡的重要 miRNA 及其靶基因。
方法
从基因表达综合数据库中获取数据集 GSE63492。使用 Limma 包和 miRWalk2.0 数据库分别识别差异表达的 miRNA（DEMs）及其靶基因。使用 R 中的 clusterProfiler 包对这些靶基因进行功能富集分析。然后，使用 STRING 数据库和 MCODE 分别进行核心调控基因的蛋白质-蛋白质相互作用（PPI）网络和子网聚类。进一步使用 Cytoscape 可视化关键 miRNA 的共调控网络和 PPI 网络。最后，鉴定细胞凋亡相关途径以及这些途径中富集的基因。
结果
上调 miRNA（hsa-miR-302c-5p、hsa-miR-631、hsa-let-7f-1-3p、hsa-miR-3675-3p 和 hsa-miR-585-3p）和下调 miRNA（hsa-miR-185-5p、hsa-miR-486-5p、hsa-miR-4306 和 hsa-miR-4674）的靶基因与细胞凋亡相关途径相关。MAPK1 和 MAPK3 是 hsa-miR-185-5p 的靶基因，而 GSK3B 是 hsa-miR-4306、hsa-miR-486-5p、hsa-miR-185-5p、hsa-let-7f-1-3p 和 hsa-miR-631 的靶基因。此外，MAPK3 和 VEGFA 分别受 hsa-miR-3675-3p 和 hsa-miR-631 调控。
结论
GSK3B 的表达可能受到 miR-4306、miR-185-5p、miR-486-5p、hsa-let-7f-1-3p 和 miR-631 的共同调控，并可能影响 IDD 的发生发展。此外，miR-185-5p 和 miR-3675-3p 可能通过 MAPK 信号通路调控 IDD 患者的髓核细胞凋亡。VEGFA 的表达可能受 miR-631 调控，有助于维持 IDD 患者的髓核细胞存活。我们的研究结果可能有助于指导进一步研究 miRNA 在 IDD 进展中的作用。
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