Research Paper Volume 16, Issue 12 pp 10380—10401
Therapeutic targets of formononetin for treating prostate cancer at the single-cell level
- 1 Department of Urology Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin, PR China
- 2 Key Laboratory of Environmental Pollution and Integrative Omics, Guilin Medical University, Education Department of Guangxi Zhuang Autonomous Region, Guilin Medical University, Guilin, PR China
- 3 Guilin Medical University, Guilin, PR China
Received: November 15, 2023 Accepted: April 22, 2024 Published: June 13, 2024
https://doi.org/10.18632/aging.205935How to Cite
Copyright: © 2024 Li 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
Prostate cancer is one of the serious health problems of older male, about 13% of male was affected by prostate cancer. Prostate cancer is highly heterogeneity disease with complex molecular and genetic alterations. So, targeting the gene candidates in prostate cancer in single-cell level can be a promising approach for treating prostate cancer. In the present study, we analyzed the single cell sequencing data obtained from 2 previous reports to determine the differential gene expression of prostate cancer in single-cell level. By using the network pharmacology analysis, we identified the therapeutic targets of formononetin in immune cells and tissue cells of prostate cancer. We then applied molecular docking to determine the possible direct binding of formononetin to its target proteins. Our result identified a cluster of differential gene expression in prostate cancer which can serve as novel biomarkers such as immunoglobulin kappa C for prostate cancer prognosis. The result of network pharmacology delineated the roles of formononetin’s targets such CD74 and THBS1 in immune cells’ function of prostate cancer. Also, formononetin targeted insulin receptor and zinc-alpha-2-glycoprotein which play important roles in metabolisms of tissue cells of prostate cancer. The result of molecular docking suggested the direct binding of formononetin to its target proteins including INSR, TNF, and CXCR4. Finally, we validated our findings by using formononetin-treated human prostate cancer cell DU145. For the first time, our result suggested the use of formononetin for treating prostate cancer through targeting different cell types in a single-cell level.