Selected Ideal Natural Ligand Against TNBC by Inhibiting CDC20, Using Bioinformatics and Molecular Biology

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2021 Oct 23

PMID 34686627

Citations 3

Authors

Naimeng Liu

Xinhui Wang

Zhu Zhu

Duo Li

Xiaye Lv

Yichang Chen

Haoqun Xie

Zhen Guo

Dong Song

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Dissection of triple-negative breast cancer microenvironment and identification of potential therapeutic drugs using single-cell RNA sequencing analysis.

Cheng W, Mi W, Wang S, Wang X, Jiang H, Chen J J Pharm Anal. 2024; 14(8):100975.

PMID: 39263352 PMC: 11388705. DOI: 10.1016/j.jpha.2024.100975.

The potential role of CDC20 in tumorigenesis, cancer progression and therapy: A narrative review.

Xian F, Zhao C, Huang C, Bie J, Xu G Medicine (Baltimore). 2023; 102(36):e35038.

PMID: 37682144 PMC: 10489547. DOI: 10.1097/MD.0000000000035038.

Structure-based virtual screening for identification of potential CDC20 inhibitors and their therapeutic evaluation in breast cancer.

Das A, Sharma H, Lather V, Pandita D, Agarwal P 3 Biotech. 2023; 13(5):141.

PMID: 37124982 PMC: 10133423. DOI: 10.1007/s13205-023-03554-7.

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