Comprehensive genomic analysis of puerarin in inhibiting bladder urothelial carcinoma cell proliferation and migration

Yu-Yang Ma; Ge-Jin Zhang; Peng-Fei Liu; Ying Liu; Ji-Cun Ding; Hao Xu; Lin Hao; Deng Pan; Hai-Luo Wang; Jing-Kai Wang; Peng Xu; Zhen-Duo Shi; Kun Pang

doi:10.2174/1574892819666230908110107

Comprehensive genomic analysis of puerarin in inhibiting bladder urothelial carcinoma cell proliferation and migration

Recent Pat Anticancer Drug Discov. 2023 Sep 8. doi: 10.2174/1574892819666230908110107. Online ahead of print.

Authors

Yu-Yang Ma^{1

2}, Ge-Jin Zhang³, Peng-Fei Liu^{4

5}, Ying Liu⁶, Ji-Cun Ding⁷, Hao Xu², Lin Hao¹, Deng Pan², Hai-Luo Wang¹, Jing-Kai Wang⁸, Peng Xu⁸, Zhen-Duo Shi^{1

2}, Kun Pang¹

Affiliations

¹ Department of Urology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical College. No.199, South Jiefang Road, Xuzhou, Jiangsu, China.
² Graduate School, Bengbu Medical College, Building 1, Administration Building, 2600 Donghai Avenue, Bengbu City, Anhui Province, China.
³ Department of Urology, Suqian Zhongwu Hospital. No. 3786, Development Avenue, Suqian Economic and Technological Development Zone, Suqian, China.
⁴ Jiangsu Provincial Key Laboratory of Educational Big Data Science and Engineering, Jiangsu Normal University, 101 Shanghai Road, Tongshan, Xuzhou 221116, China.
⁵ School of Mathematics and Statistics and Research Institute of Mathematical Sciences (RIMS), Jiangsu Normal University, 101 Shanghai Road, Tongshan, Xuzhou 221116, China.
⁶ Department of Laboratory, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical College. No.199, South Jiefang Road, Xuzhou, Jiangsu, China.
⁷ Department of Burn and Plastic Surgery, Xuzhou First People's Hospital. No. 269, Daxue Road, Tongshan District, Xuzhou, Jiangsu, China.
⁸ Graduate School, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu Province, China.

PMID: 37694778
DOI: 10.2174/1574892819666230908110107

Abstract

Background: Bladder urothelial carcinoma (BUC) ranks second in the incidence of urogenital system tumors, and the treatment of BUC needs to be improved. Puerarin, a traditional Chinese medicine (TCM), has been shown to have various effects such as anti-cancer effects, the promotion of angiogenesis, and anti-inflammation. This study investigates the effects of puerarin on BUC and its molecular mechanisms.

Methods: Through GeneChip experiments, we obtained differentially expressed genes (DEGs) and analyzed these DEGs using the Ingenuity® Pathway Analysis (IPA®), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses. The Cell Counting Kit 8 (CCK8) assay was used to verify the inhibitory effect of puerarin on the proliferation of BUC T24 cells. String combined with Cytoscape® was used to create the Protein-Protein Interaction (PPI) network, and the MCC algorithm in cytoHubba plugin was used to screen key genes. Gene Set Enrichment Analysis (GSEA®) was used to verify the correlation between key genes and cell proliferation.

Results: A total of 1617 DEGs were obtained by GeneChip. Based on the DEGs, the IPA® and pathway enrichment analysis showed they were mainly enriched in cancer cell proliferation and migration. CCK8 experiments proved that puerarin inhibited the proliferation of BUC T24 cells, and its IC50 at 48 hours was 218µmol/L. Through PPI and related algorithms, 7 key genes were obtained: ITGA1, LAMA3, LAMB3, LAMA4, PAK2, DMD, and UTRN. GSEA showed that these key genes were highly correlated with BUC cell proliferation. Survival curves showed that ITGA1 upregulation was associated with poor prognosis of BUC patients.

Conclusion: Our findings support the potential antitumor activity of puerarin in BUC. To the best of our knowledge, bioinformatics investigation suggests that puerarin demonstrates anticancer mechanisms via the upregulation of ITGA1, LAMA3 and 4, LAMB3, PAK2, DMD, and UTRN, all of which are involved in the proliferation and migration of bladder urothelial cancer cells.

Keywords: Bladder Urothelial Carcinoma (BUC); Puerarin; bioinformatics; migration; proliferation; protein–protein interaction.