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Using single-cell sequencing data from two prior studies, the work profiles differential gene expression and applies network pharmacology to identify formononetin therapeutic targets in immune and tissue cells.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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\nTherapeutic targets of formononetin for treating prostate cancer at the single-cell level  \nJiawei Li 1, Zhaoquan Huang3, Ping Wang2, Rong Li2, Li Gao1, Keng Po Lai2  \n1 Department of Urology Surgery, The Second Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin, PR China  \n2 Key Laboratory of Environmental Pollution and Integrative Omics, Guilin Medical University, Education Department of Guangxi Zhuang Autonomous Region, Guilin Medical University, Guilin, PR China 3Guilin Medical University, Guilin, PR China  \nCorrespondence to: Li Gao, Keng Po Lai; [email:](email: 40407864@qq.com)[ ](email: 40407864@qq.com)[40407864@qq.com](email: 40407864@qq.com), [https://orcid.org/0009-0009-0626-9290](https://orcid.org/0009-0009-0626-9290); [kengplai@glmc.edu.cn](kengplai@glmc.edu.cn)  \nKeywords: network pharmacology, formononetin, prostate cancer, single cell, therapeutic targets, immune response, heterogeneity  \nReceived: November 15, 2023 Accepted: April 22, 2024 Published: June 13, 2024  \nCopyright: © 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.  \nABSTRACT  \nProstate 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.  \nINTRODUCTION  \nProstate cancer ranks as the second most common cancer in men after lung cancer, posing a serious threat to the life and health of middle-aged and elderly men [1] . And, it is one of the leading causes of cancerrelated deaths in men. Early symptoms of prostate cancer are not obvious, and most early diagnoses of prostate cancer are detected by prostate-specific antigen (PSA) screening and magnetic resonance imaging (MRI)  \n[2] . The symptoms present in each patient are variable, due to the heterogeneity of prostate cancer, in which, the size of the tumor, the degree of malignancy, and metastatic ability are different [3] . Also, the high tumour heterogeneity in prostate cancer was a challenge for clinical disease management and a serious problem for molecular stratification of patients [4] . Single-cell RNA sequencing (scRNA-seq) method can analyze tumor tissue heterogeneity on a large scale and at","cbCaiidlREjOt1tB","https://ap.wps.com/l/cbCaiidlREjOt1tB","pdf",1919464,22,"English","# Abstract\n# Introduction\n## Prostate cancer burden and heterogeneity\n## Single-cell RNA sequencing for precision profiling\n## Current treatment options and need for new therapies\n## Estrogen receptors and formononetin as candidate therapeutics","[{\"question\":\"Why is prostate cancer considered challenging to treat?\",\"answer\":\"Prostate cancer is highly heterogeneous, with variable tumor size, malignancy grade, and metastatic potential, making molecular stratification and management difficult.\"},{\"question\":\"How did the study identify targets of formononetin at the single-cell level?\",\"answer\":\"It analyzed single-cell RNA sequencing data from two previous reports to find differential gene expression, then used network pharmacology to identify therapeutic targets in immune and tissue cells.\"},{\"question\":\"What methods were used to support target–compound relationships?\",\"answer\":\"Molecular docking was applied to evaluate possible direct binding between formononetin and predicted target proteins, followed by cellular validation using formononetin-treated DU145 prostate cancer cells.\"}]","Therapeutic targets of formononetin for treating prostate cancer at the single-cell level | PDF",1790002846,55]