Department of Orthopedics, the First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai, China.
J Transl Med. 2022 Feb 15;20(1):93. doi: 10.1186/s12967-022-03295-w.
This study aimed to use bioinformatics methods to characterize epigenetic changes in terms of micro-RNA(miRNA) expression and DNA methylation during adipogenesis. The mRNA and miRNA expression microarray and DNA methylation dataset were obtained from the GEO database. Differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs) and differentially methylated probes (DMPs) were filtered using the limma package. The R language cluster profile package was used for functional and enrichment analysis. A protein-protein interaction (PPI) network was constructed using STRING and visualized in Cytoscape. The Connection map (CMap) website tool was used to screen potential therapeutic drugs for adipogenesis. When comparing the early and late stages of adipogenesis, 111 low miRNA targeted upregulated genes and 64 high miRNA targeted downregulated genes were obtained, as well as 663 low-methylated high-expressed genes and 237 high-methylated low-expressed genes. In addition, 41 genes (24 upregulated and 17 downregulated) were simultaneously regulated by abnormal miRNA changes and DNA methylation. Ten chemicals were identified as putative therapeutics for adipogenesis. In addition, among the dual-regulated genes identified, CANX, HNRNPA1, MCL1, and PPIF may play key roles in the epigenetic regulation of adipogenesis and may serve as aberrant methylation or miRNA targeting biomarkers.
本研究旨在使用生物信息学方法,从 miRNA 表达和 DNA 甲基化角度描述脂肪生成过程中的表观遗传变化。mRNA 和 miRNA 表达微阵列及 DNA 甲基化数据集从 GEO 数据库中获得。使用 limma 包筛选差异表达基因(DEGs)、差异表达 miRNA(DEMs)和差异甲基化探针(DMPs)。使用 R 语言 cluster profile 包进行功能和富集分析。使用 STRING 构建蛋白质-蛋白质相互作用(PPI)网络,并在 Cytoscape 中可视化。使用 Connection map(CMap)网站工具筛选潜在的脂肪生成治疗药物。在比较脂肪生成的早期和晚期时,获得了 111 个低 miRNA 靶向上调基因和 64 个高 miRNA 靶向下调基因,以及 663 个低甲基化高表达基因和 237 个高甲基化低表达基因。此外,有 41 个基因(24 个上调和 17 个下调)同时受到异常 miRNA 变化和 DNA 甲基化的调控。确定了 10 种化学物质可能是脂肪生成的潜在治疗药物。此外,在鉴定的双调控基因中,CANX、HNRNPA1、MCL1 和 PPIF 可能在脂肪生成的表观遗传调控中发挥关键作用,并且可能作为异常甲基化或 miRNA 靶向的生物标志物。