Database screening of herbal monomers regulating autophagy by constructing a "disease-gene-drug" network.

Database screening of herbal monomers regulating autophagy by constructing a "disease-gene-drug" network.
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通过构建“疾病-基因-药物”网络对调节自噬的草药单体进行数据库筛选。

DOI:
10.1186/1472-6882-14-466
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发表时间:
2014-12-04
影响因子:
--
通讯作者:
Zhang W
Zhang W
中科院分区:
医学3区
文献类型:
--
作者:
Hao C;Yang Z;Gao B;Lu M;Meng X;Qiao X;Xue D;Zhang W

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研究表明,自噬作为癌症治疗的靶点具有重要作用。我们利用生物信息学的模块化方法构建了“疾病-基因-药物”网络,并筛选了展示与自噬调节相关功能的草药单体。基于基因表达总表(GEO)数据库(GSE2435和GSE31040,饥饿诱导自噬模型)的微阵列结果,我们使用人类蛋白质参考数据库(HPRD)来获得蛋白质-蛋白质相互作用(PPI)网络。此外,我们使用CFinder软件确定了几个功能模块,使用David软件进行了基因本体-生物学过程(GO-BP)功能富集化分析,利用文献检索和Cytosscape软件构建了草药单体-模块基因调控网络,并分析了自噬、基因和草药单体之间的关系。我们筛选了544个与自噬相关的差异表达基因,375对差异表达基因,以及7个基因模块,其中模块3(由7个基因组成)的功能在细胞死亡中得到了丰富。利用构建的草药单体-模块基因调控网络,我们发现30个草药单体可以同时调控这7个基因,这表明自噬具有潜在的调控作用。利用疾病-基因-药物网络进行数据库筛选,可以为中草药在癌症治疗中的应用提供新的策略和思路。
Studies suggest an important role of autophagy as a target for cancer therapy. We constructed a "disease-gene-drug" network using the modular approach of bioinformatics and screened herbal monomers demonstrating functions related to autophagy regulation. Based on the microarray results of the gene expression omnibus (GEO) database (GSE2435 and GSE31040, starvation-induced autophagy model), we used the human protein reference database (HPRD) to obtain the protein-protein interaction (PPI) network. In addition, we used the CFinder software to identify several functional modules, performed gene ontology-biological process (GO-BP) functional enrichment analysis using the DAVID software, constructed a herbal monomer-module gene regulatory network using literature search and the Cytoscape software, and then analyzed the relationships between autophagy, genes, and herbal monomers. We screened 544 differentially expressed genes related to autophagy, 375 pairs of differentially expressed genes, and 7 gene modules, wherein the functions of module 3 (composed of 7 genes) were enriched in "cell death". Using the constructed herbal monomer-module gene regulatory network, we found that 30 herbal monomers can simultaneously regulate these 7 genes, indicating a potential regulatory role in autophagy. Database screening using the disease-gene-drug network can provide new strategies and ideas for the application of herbal medicines in cancer therapy.
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