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RNA-Sequencing, Connectivity Mapping, and Molecular Docking to Investigate Ligand-Protein Binding for Potential Drug Candidates for the Treatment of Wilms Tumor.

Abstract：

:BACKGROUND Wilms tumor, or nephroblastoma, is a malignant pediatric embryonal renal tumor that has a poor prognosis. This study aimed to use bioinformatics data, RNA-sequencing, connectivity mapping, molecular docking, and ligand-protein binding to identify potential targets for drug therapy in Wilms tumor. MATERIAL AND METHODS Wilms tumor and non-tumor samples were obtained from high throughput gene expression databases, and differentially expressed genes (DEGs) were analyzed using the voom method in the limma package. The overlapping DEGs were obtained from the intersecting drug target genes using the Connectivity Map (CMap) database, and systemsDock was used for molecular docking. Gene databases were searched for gene expression profiles for complementary analysis, analysis of clinical significance, and prognosis analysis to refine the study. RESULTS From 177 cases of Wilms tumor, there were 648 upregulated genes and 342 down-regulated genes. Gene Ontology (GO) enrichment analysis showed that the identified DEGs that affected the cell cycle. After obtaining 21 candidate drugs, there were seven overlapping genes with 75 drug target genes and DEGs. Molecular docking results showed that relatively high scores were obtained when retinoic acid and the cyclin-dependent kinase inhibitor, alsterpaullone, were docked to the overlapping genes. There were significant standardized mean differences for three overlapping genes, CDK2, MAP4K4, and CRABP2. However, four upregulated overlapping genes, CDK2, MAP4K4, CRABP2, and SIRT1 had no prognostic significance. CONCLUSIONS RNA-sequencing, connectivity mapping, and molecular docking to investigate ligand-protein binding identified retinoic acid and alsterpaullone as potential drug candidates for the treatment of Wilms tumor.

journal_name

Med Sci Monit

journal_title

Medical science monitor : international medical journal of experimental and clinical research

authors

Luo JY,Yan SB,Chen G,Chen P,Liang SW,Xu QQ,Gu JH,Huang ZG,Qin LT,Lu HP,Mo WJ,Luo YG,Chen JB

doi

10.12659/MSM.920725

subject

Has Abstract

pub_date

2020-03-26 00:00:00

pages

e920725

eissn

1234-1010

issn

1643-3750

pii

920725

journal_volume

pub_type

杂志文章

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RNA-Sequencing, Connectivity Mapping, and Molecular Docking to Investigate Ligand-Protein Binding for Potential Drug Candidates for the Treatment of Wilms Tumor.