Research Paper Volume 13, Issue 20 pp 23702—23725

Selected ideal natural ligand against TNBC by inhibiting CDC20, using bioinformatics and molecular biology

Naimeng Liu1, , Xinhui Wang2, , Zhu Zhu1, , Duo Li4, , Xiaye Lv3, , Yichang Chen1, , Haoqun Xie5, , Zhen Guo5, , Dong Song1, ,

  • 1 Department of Breast Surgery, The First Hospital of Jilin University, Changchun, China
  • 2 Department of Oncology, First People’s Hospital of Xinxiang, Xinxiang, China
  • 3 Department of Hematology, The First Clinical Medical School of Lanzhou University, Lanzhou, Gansu, China
  • 4 Department of General Surgery, China-Japan Friendship Hospital, Beijing, China
  • 5 Clinical College, Jilin University, Changchun, China

Received: July 28, 2021       Accepted: September 29, 2021       Published: October 22, 2021
How to Cite

Copyright: © 2021 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Object: Find potential therapeutic targets of triple-negative breast cancer (TNBC) patients by bioinformatics. Screen ideal natural ligand that can bind with the potential target and inhibit it by using molecular biology.

Methods: Bioinformatics and molecular biology were combined to analyze potential therapeutic targets. Differential expression analysis identified the differentially expressed genes (DEGs) between TNBC tissues and non-TNBC tissues. The functional enrichment analyses of DEGs shown the important gene ontology (GO) terms and pathways of TNBC. Protein-protein interaction (PPI) network construction screened 20 hub genes, while Kaplan website was used to analyze the relationship between the survival curve and expression of hub genes. Then Discovery Studio 4.5 screened ideal natural inhibitors of the potential therapeutic target by LibDock, ADME, toxicity prediction, CDOCKER and molecular dynamic simulation.

Results: 1,212 and 353 DEGs were respectively found between TNBC tissues and non-TNBC tissues, including 88 up-regulated and 141 down-regulated DEGs in both databases. 20 hub genes were screened, and the higher expression of CDC20 was associated with a poor prognosis. Therefore, we chose CDC20 as the potential therapeutic target. 7,416 natural ligands were conducted to bind firmly with CDC20, and among these ligands, ZINC000004098930 was regarded as the potential ideal ligand, owing to its non-hepatotoxicity, more solubility level and less carcinogenicity than the reference drug, apcin. The ZINC000004098930-CDC20 could exist stably in natural environment.

Conclusion: 20 genes were regarded as hub genes of TNBC and most of them were relevant to the survival curve of breast cancer patients, especially CDC20. ZINC000004098930 was chosen as the ideal natural ligand that can targeted and inhibited CDC20, which may give great contribution to TNBC targeted treatment.


TNBC: Triple-negative breast cancer; DEGs: Differentially expressed genes; PPI: Protein-protein interaction; ER: Estrogen receptor; PR: Progesterone receptor; HER2: Human epidermal growth factor receptor 2; PI3K: Dysregulation of phosphoinositide 3 kinase; GEO: Gene Expression Omnibus; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; DAVID: Database for Annotation, Visualization and Integrated Discovery; BP: Biological processes; MF: Molecular functions; CC: Cellular components; STRING: Search Tool for the Retrieval of Interacting Genes; OS: Overall survival; RFS: Recurrence-free survival; ADME: Absorption distribution metabolic excretion; BBB level: Blood brain barrier level; CYP2D6: Cytochrome P450 2D6 inhibition; PPB level: Plasma protein binding properties level; DTP: Developmental toxicity potential; NTP: National Toxicology Program dataset; CDC20: Cell-division cycle protein 20 homologue; HB: Hydrogen bond; APC/C: Anaphase-promoting complex/cyclosome; TAME: Tosyl-L-arginine methyl ester; TCGA: The Cancer Genome Atlas.