Wang Dengchuan, Liu Shengshuo, Xu Shi
Office of Medical Ethics, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong.
School of Pharmacy, Henan University, Kaifeng, Henan, China.
Medicine (Baltimore). 2020 Feb;99(7):e19022. doi: 10.1097/MD.0000000000019022.
Hutchinson-Gilford Progeria syndrome (HGPS) is a rare lethal premature and accelerated aging disease caused by mutations in the lamin A/C gene. Nevertheless, the mechanisms of cellular damage, senescence, and accelerated aging in HGPS are not fully understood. Therefore, we aimed to screen potential key genes, pathways, and therapeutic agents of HGPS by using bioinformatics methods in this study.
The gene expression profile of GSE113648 and GSE41751 were retrieved from the gene expression omnibus database and analyzed to identify the differentially expressed genes (DEGs) between HGPS and normal controls. Then, gene ontology and the Kyoto encyclopedia of genes and genomes pathway enrichment analysis were carried out. To construct the protein-protein interaction (PPI) network, we used STRING and Cytoscape to make module analysis of these DEGs. Besides, the connectivity map (cMAP) tool was used as well to predict potential drugs.
As a result, 180 upregulated DEGs and 345 downregulated DEGs were identified, which were significantly enriched in pathways in cancer and PI3K-Akt signaling pathway. The top centrality hub genes fibroblast growth factor 2, decorin, matrix metallopeptidase2, and Fos proto-oncogene, AP-1 transcription factor subunit were screened out as the critical genes among the DEGs from the PPI network. Dexibuprofen and parthenolide were predicted to be the possible agents for the treatment of HGPS by cMAP analysis.
This study identified key genes, signal pathways and therapeutic agents, which might help us improve our understanding of the mechanisms of HGPS and identify some new therapeutic agents for HGPS.
哈钦森 - 吉尔福德早衰综合征（HGPS）是一种由核纤层蛋白A/C基因突变引起的罕见致死性早衰和加速衰老疾病。然而，HGPS中细胞损伤、衰老和加速衰老的机制尚未完全明确。因此，本研究旨在运用生物信息学方法筛选HGPS的潜在关键基因、信号通路和治疗药物。
从基因表达综合数据库中检索GSE113648和GSE41751的基因表达谱，并进行分析以鉴定HGPS与正常对照之间的差异表达基因（DEG）。然后，进行基因本体论和京都基因与基因组百科全书通路富集分析。为构建蛋白质 - 蛋白质相互作用（PPI）网络，我们使用STRING和Cytoscape对这些DEG进行模块分析。此外，还使用连通性图谱（cMAP）工具预测潜在药物。
结果鉴定出180个上调的DEG和345个下调的DEG，它们在癌症通路和PI3K - Akt信号通路中显著富集。从PPI网络的DEG中筛选出中心性最高的枢纽基因成纤维细胞生长因子2、核心蛋白聚糖、基质金属蛋白酶2和原癌基因Fos、AP - 1转录因子亚基作为关键基因。通过cMAP分析预测右布洛芬和小白菊内酯可能是治疗HGPS的药物。
本研究鉴定出关键基因、信号通路和治疗药物，这可能有助于我们加深对HGPS机制的理解，并为HGPS确定一些新的治疗药物。
