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The Potential Mechanism of Bufadienolide-Like Chemicals on Breast Cancer via Bioinformatics Analysis

文献类型： 外文期刊

作者： Zhang, Yingbo 1 ; Tang, Xiaomin 3 ; Pang, Yuxin 3 ; Huang, Luqi 5 ; Wang, Dan 1 ; Yuan, Chao 1 ; Hu, Xuan 1 ; Qu, Liping;

作者机构： 1.Chinese Acad Trop Agr Sci, Trop Crops Genet Resources Inst, Danzhou 571737, Peoples R China

2.Hainan Prov Engn Res Ctr Blumea Balsamifera, Danzhou 571737, Peoples R China

3.Guangdong Pharmaceut Univ, Sch Tradit Chinese Med, Guangzhou 510006, Guangdong, Peoples R China

4.China Acad Chinese Med Sci, Natl Resource Ctr Chinese Mat Med, Beijing 100700, Peoples R China

5.China Acad Chinese Med Sci, Natl Resource Ctr Chin

关键词： Bufadienolide-like chemicals; molecular mechanism; anti-cancer; bioinformatics

期刊名称：CANCERS （ 影响因子：6.639； 五年影响因子：6.999 ）

ISSN： 2072-6694

年卷期： 2019 年 11 卷 1 期

页码：

收录情况： SCI

摘要： Bufadienolide-like chemicals are mostly composed of the active ingredient of Chansu and they have anti-inflammatory, tumor-suppressing, and anti-pain activities; however, their mechanism is unclear. This work used bioinformatics analysis to study this mechanism via gene expression profiles of bufadienolide-like chemicals: (1) Differentially expressed gene identification combined with gene set variation analysis, (2) similar small -molecule detection, (3) tissue-specific co-expression network construction, (4) differentially regulated sub-networks related to breast cancer phenome, (5) differentially regulated sub-networks with potential cardiotoxicity, and (6) hub gene selection and their relation to survival probability. The results indicated that bufadienolide-like chemicals usually had the same target as valproic acid and estradiol, etc. They could disturb the pathways in RNA splicing, the apoptotic process, cell migration, extracellular matrix organization, adherens junction organization, synaptic transmission, Wnt signaling, AK-STAT signaling, BMP signaling pathway, and protein folding. We also investigated the potential cardiotoxicity and found a dysregulated subnetwork related to membrane depolarization during action potential, retinoic acid receptor binding, GABA receptor binding, positive regulation of nuclear division, negative regulation of viral genome replication, and negative regulation of the viral life cycle. These may play important roles in the cardiotoxicity of bufadienolide-like chemicals. The results may highlight the potential anticancer mechanism and cardiotoxicity of Chansu, and could also explain the ability of bufadienolide-like chemicals to be used as hormones and anticancer and vasoprotectives agents.

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