Title:Exploring the Molecular Mechanisms of Huaier on Modulating Metabolic
Reprogramming of Hepatocellular Carcinoma: A Study based on Network
Pharmacology, Molecular Docking and Bioinformatics
Volume: 30
Issue: 24
Author(s): Yuxiang Wan, Honglin Jiang, Zeyu Liu, Chen Bai, Yanyan Lian, Chunguang Zhang, Qiaoli Zhang*Jinchang Huang*
Affiliation:
- Department of Acupuncture and Mini-invasive Oncology, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, 100029, China
- Department of Acupuncture and Mini-invasive Oncology, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, 100029, China
Keywords:
Huaier, hepatocellular carcinoma, AKRIC3, network pharmacology, metabolic reprogramming, traditional Chinese medicine.
Abstract:
Background: Huaier (Trametes robiniophila Murr), a traditional Chinese medicine, is widely used
in China as a complementary and alternative therapy to treat hepatocellular carcinoma (HCC). Past studies
have shown that Huaier can arrest the cell cycle, promote apoptosis and inhibit the proliferation of cancer
cells. However, how it regulates the metabolism of HCC is still unclear.
Objective: This study explores the metabolic-related function of Huaier in treating HCC with an in-silico approach.
Methods: A network pharmacology and bioinformatics-based approach was employed to investigate the
molecular pathogenesis of metabolic reprogramming in HCC with Huaier. The compounds of Huaier were obtained
from public databases. Oral bioavailability and drug likeness were screened using the TCMSP platform.
The differential gene expressions between HCC and non-tumor tissue were calculated and used to find the
overlap from the targets of Huaier. The enrichment analysis of the overlapped targets by Metascape helped filter
out the metabolism-related targets of Huaier in treating HCC. Protein-protein interaction (PPI) network construction
and topological screening revealed the hub nodes. The prognosis and clinical correlation of these targets
were validated from the cancer genome atlas (TCGA) database, and the interactions between the hub
nodes and active ingredients were validated by molecular docking.
Results: The results showed that Peroxyergosterol, Daucosterol, and Kaempferol were the primary active compounds
of Huaier involved in the metabolic reprogramming of HCC. The top 6 metabolic targets included
AKR1C3, CYP1A1, CYP3A4, CYP1A2, CYP17A1, and HSD11B1. The decreased expression of CYP3A4
and increased expression of AKR1C3 were related to the poor overall survival of HCC patients. The molecular
docking validated that Peroxyergosterol and Kaempferol exhibited the potential to modulate CYP3A4 and
AKR1C3 from a computational perspective.
Conclusion: This study provided a workflow for understanding the mechanism of Huaier in regulating the
metabolic reprogramming of HCC.
