Research Paper Volume 15, Issue 24 pp 15267—15286
Integrative transcriptome and single-cell sequencing technology analysis of the potential therapeutic benefits of oleanolic acid in liver injury and liver cancer
- 1 Department of Abdominal Surgery, Guiqian International General Hospital, Guiyang, Guizhou, China
- 2 Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
- 3 Department of Thoracic Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
- 4 Department of Hepatobiliary and Pancreatic Surgery II, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
Received: July 19, 2023 Accepted: November 11, 2023 Published: December 20, 2023
https://doi.org/10.18632/aging.205349How to Cite
Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Oleanolic acid has important hepatoprotective effects and inhibits liver tissue carcinogenesis. The aim of this study was to investigate the mechanism of action of oleanolic acid in inhibiting liver injury and liver cancer.
Method: In this study, we applied differential gene analysis and gene enrichment analysis to identify the targets of oleanolic acid for the treatment of liver injury. And this study also applied Cibersort and GSVA methods to investigate the targets of oleanolic acid in liver injury. Based on oleanolic acid targets, we explored the major targets and further explored the role of the major targets in liver cancer. This study used the oncoPredict and the TIDE algorithm to predict the effect of oleanolic acid on drug resistance. Finally, the binding effect of oleanolic acid to relevant targets was explored using molecular docking techniques.
Result: In this study, oleanolic acid was found to inhibit liver injury and promote liver regeneration mainly by promoting elevated expression of HMOX1. Oleanolic acid can inhibit oxidative stress and promotes Ferroptosis in liver injury. In liver cancer, we identified that the main target of oleanolic acid is HMOX1 and HDAC1. And we determined that HMOX1 promotes Ferroptosis in liver cancer. This reduced the sensitivity of liver cancer to targeted therapies and immunotherapy. Molecular docking showed high binding of oleanolic acid to HDAC1 and HMOX1.
Conclusions: Oleanolic acid is an antioxidant by promoting high expression of HMOX1 and promotes the development of Ferroptosis in liver cancer and liver injury.