Exploring the Molecular Mechanisms of Huaier on Modulating Metabolic Reprogramming of Hepatocellular Carcinoma: A Study based on Network Pharmacology, Molecular Docking and Bioinformatics


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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.

About the authors

Yuxiang Wan

Department of Acupuncture and Mini-invasive Oncology, Beijing University of Chinese Medicine Third Affiliated Hospital,

Email: info@benthamscience.net

Honglin Jiang

Department of Acupuncture and Mini-invasive Oncology, Beijing University of Chinese Medicine Third Affiliated Hospital

Email: info@benthamscience.net

Zeyu Liu

Department of VIP Region, Sun Yat-sen University Cancer Center

Email: info@benthamscience.net

Chen Bai

School of Traditional Chinese Medicine,, Beijing University of Chinese Medicine

Email: info@benthamscience.net

Yanyan Lian

Department of Acupuncture and Mini-invasive Oncology, Beijing University of Chinese Medicine Third Affiliated Hospital

Email: info@benthamscience.net

Chunguang Zhang

Department of Acupuncture and Mini-invasive Oncology, Beijing University of Chinese Medicine Third Affiliated Hospital

Email: info@benthamscience.net

Qiaoli Zhang

Department of Acupuncture and Mini-invasive Oncology, Beijing University of Chinese Medicine Third Affiliated Hospital

Author for correspondence.
Email: info@benthamscience.net

Jinchang Huang

Department of Acupuncture and Mini-invasive Oncology, Beijing University of Chinese Medicine Third Affiliated Hospital

Author for correspondence.
Email: info@benthamscience.net

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