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Molecular mechanisms of Tanshinone IIA in Hepatocellular carcinoma therapy via WGCNA-based network pharmacology analysis

HAN ZHAO1, JING GUO1, QINGJIA CHI2, MENG FANG1,*

1 School of Medicine, Jianghan University, Wuhan, 430056, China
2 Department of Mechanics and Engineering Structure, Wuhan University of Technology, Wuhan, 430070, China

* Address correspondence to: Meng Fang,

BIOCELL 2022, 46(5), 1245-1259. https://doi.org/10.32604/biocell.2022.018117

Abstract

Hepatocellular carcinoma (HCC) is a worldwide malignant tumor that caused irreversible consequences. Tanshinone IIA has been shown to play a notable role in HCC treatment. However, the potential targets and associating mechanism of Tanshinone IIA against HCC remain unknown. We first screened out 105 overlapping genes by integrating the predicted targets of Tanshinone IIA from multiple databases and the differentially expressed genes of HCC from the Cancer Genome Atlas (TCGA) database. Then, we performed weighted gene co-expression network analysis (WGCNA) using the RNA-seq profiles of overlapping genes and HCC-related clinical information. 23 genes related to clinical tumor grade in the important module were imported for Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) analysis. Comparing the key genes in the important module from WGCNA with the high connectivity nodes from the PPI network, we identified three hub genes, AURKB, KIF11, and PLK1. For further verification, we tested the binding of Tanshinone IIA to three hub genes. The survival curve, receiver operating characteristic (ROC) curve, mRNA expression, and protein expression were also used to validate the hub genes. In the study, WGCNA revealed grade-specific gene modules, and the following KEGG pathway analysis indicated that Tanshinone IIA probably plays therapeutical effect in the development of HCC, especially in the cell cycle. Our result partially explained the pharmacological mechanism of Tanshinone IIA against HCC.

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ZHAO, H., GUO, J., CHI, Q., FANG, M. (2022). Molecular mechanisms of Tanshinone IIA in Hepatocellular carcinoma therapy via WGCNA-based network pharmacology analysis. BIOCELL, 46(5), 1245–1259.



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