Quercetin inhibits proliferation and migration of clear cell renal cell carcinoma cells by regulating TP53 gene.
10.12122/j.issn.1673-4254.2025.02.12
- Author:
Junjie GAO
1
;
Kai YE
1
;
Jing WU
1
Author Information
1. Department of Laboratory Medicine, Second Affiliated Hospital of Wannan Medical College, Wuhu 241000, China.
- Publication Type:Journal Article
- Keywords:
Mendelian randomization;
TP53 gene;
molecular targets;
network pharmacology;
quercetin;
renal clear cell carcinoma
- MeSH:
Humans;
Quercetin/pharmacology*;
Carcinoma, Renal Cell/genetics*;
Cell Proliferation/drug effects*;
Kidney Neoplasms/genetics*;
Cell Movement/drug effects*;
Tumor Suppressor Protein p53/metabolism*;
Cell Line, Tumor;
Computational Biology
- From:
Journal of Southern Medical University
2025;45(2):313-321
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To identify potential molecular targets of quercetin in the treatment of clear cell renal carcinoma (ccRCC).
METHODS:The therapeutic targets of quercetin were screened from multiple databases by network pharmacology analysis, and the targets significantly correlated with ccRCC were screened from 4907 plasma proteins using a Mendelian randomization method. The drug-disease network model was constructed to screen the potential key targets. The functions of these targets were evaluated via bioinformatics analysis, and the screened targets were verified in cultured ccRCC cells.
RESULTS:Network pharmacology analysis combined with Mendelian randomization identified TP53 (OR=3.325, 95% CI: 1.805-6.124, P=0.0001), ARF4 (OR=0.173, 95% CI: 0.065-0.456, P=0.0003), and DPP4 (OR=0.463, 95% CI: 0.302-0.711, P=0.0004) as the core targets in quercetin treatment of ccRCC. Bioinformatics analysis showed that TP53 was highly expressed in ccRCC, and patients with high TP53 expressions had worse survival outcomes. Molecular docking studies showed that the binding energy between quercetin and TP53 was -5.83 kcal/mol. In cultured 786-O cells, CCK-8 assay and wound healing assay showed that treatment with quercetin significantly inhibited cell proliferation and migration. Quercetin treatment also strongly suppressed the expression of TP53 at both the mRNA and protein levels in 786-O cells as shown by RT-qPCR and Western blotting.
CONCLUSIONS:TP53 may be the key target of quercetin in the treatment of ccRCC, which sheds light on potential molecular mechanism that mediate the therapeutic effect of quercetin.
