{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T14:27:59Z","timestamp":1762957679742,"version":"build-2065373602"},"reference-count":122,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study analyzes publicly available RNA-seq data to comprehensively include the complex heterogeneity of prostate cancer (PCa) etiology. It combines prostate and prostate cancer (PCa) cell lines, representing primary PCa cells, Gleason scores, ages, and PCa of different racial origins. Additionally, some cell lines were exposed to endocrine-disrupting chemicals (EDCs). The research aims to identify hub genes and transcription factors (TFs) of the prostate carcinogenesis pathway as molecular targets for clinical investigations to elucidate EDC-induced aggressiveness and to develop potential biomarkers for their exposure risk assessments. PCa cells rely on androgen receptor (AR)-mediated signaling to survive, develop, and function. Fifteen various RNA-seq datasets were normalized for distribution, and the significance (p-value &lt; 0.05) threshold of differentially expressed genes (DEGs) was set based on |log2FC| \u2265 2 change. Through integrated bioinformatics, we applied cBioPortal, UCSC-Xena, TIMER2.0, and TRRUST platforms, among others, to associate hub genes and their TFs based on their biologically meaningful roles in aggressive prostate carcinogenesis. Among all RNA-Seq datasets, we found 75 overlapping DEGs, with BUB1B (32%) and CCNB1 (29%) genes exhibiting the highest degree of mutation, amplification, and deletion. EDC-associated CCNB1, BUB1B, and CCNA2 in PCa cells exposed to EDCs were consistently shown to be associated with high Gleason scores (\u22654 + 3) and in the &gt;60 age group of patients. Selected TFs (E2F4, MYC, and YBX1) were also significantly associated with DEGs (NCAPG, MKI67, CCNA2, CCNB1, CDK1, CCNB2, AURKA, UBE2C, BUB1B) and influenced the overall survival (p-value &lt; 0.05) of PCa cases. This is one of the first comprehensive studies combining 15 publicly available RNA-seq datasets to demonstrate the association of EDC-associated hub genes and their TFs aligning with the aggressive carcinogenic pathways in the higher age group (&gt;60 years) of patients. The findings highlight the potential of these hub genes as candidates for further studies to develop molecular biomarkers for assessing the EDC-related PCa risk, diagnosing PCa aggressiveness, and identifying therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms26125463","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T12:58:21Z","timestamp":1749214701000},"page":"5463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["RNA-Seq Uncovers Association of Endocrine-Disrupting Chemicals with Hub Genes and Transcription Factors in Aggressive Prostate Cancer"],"prefix":"10.3390","volume":"26","author":[{"given":"Diaaidden","family":"Alwadi","sequence":"first","affiliation":[{"name":"Department of Environmental Health Sciences, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7151-0441","authenticated-orcid":false,"given":"Quentin","family":"Felty","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7761-1251","authenticated-orcid":false,"given":"Mayur","family":"Doke","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, University of Miami, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6409-1341","authenticated-orcid":false,"given":"Deodutta","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changwon","family":"Yoo","sequence":"additional","affiliation":[{"name":"Biostatistics Department, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3725-3971","authenticated-orcid":false,"given":"Alok","family":"Deoraj","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21654","article-title":"Cancer Statistics, 2022","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","first-page":"135","article-title":"The American Cancer Society\u2019s Facts & Figures: 2022 Edition","volume":"11","author":"Viale","year":"2020","journal-title":"J. Adv. Pract. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/j.bbamcr.2016.02.016","article-title":"The molecular and cellular origin of human prostate cancer","volume":"1863","author":"Packer","year":"2016","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s13187-018-1320-1","article-title":"Prostate Cancer Patients\u2019 Understanding of the Gleason Scoring System: Implications for Shared Decision-Making","volume":"34","author":"Tagai","year":"2018","journal-title":"J. Cancer Educ."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Messner, E.A., Steele, T.M., Tsamouri, M.M., Hejazi, N., Gao, A.C., Mudryj, M., and Ghosh, P.M. (2020). The androgen receptor in prostate cancer: Effect of structure, ligands and spliced variants on therapy. Biomedicines, 8.","DOI":"10.3390\/biomedicines8100422"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"a030478","DOI":"10.1101\/cshperspect.a030478","article-title":"New Opportunities for Targeting the Androgen Receptor in Prostate Cancer","volume":"8","author":"Centenera","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.ccr.2011.09.001","article-title":"Androgen Receptor Gene Expression in Prostate Cancer Is Directly Suppressed by the Androgen Receptor Through Recruitment of Lysine-Specific Demethylase 1","volume":"20","author":"Cai","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1756287221997186","DOI":"10.1177\/1756287221997186","article-title":"Prostate cancer biomarkers and multiparametric MRI: Is there a role for both in prostate cancer management?","volume":"13","author":"Saltman","year":"2021","journal-title":"Ther. Adv. Urol."},{"key":"ref_10","first-page":"1","article-title":"Integrative Analysis of Bulk RNA-Seq and Single-Cell RNA-Seq Unveils the Characteristics of the Immune Microenvironment and Prognosis Signature in Prostate Cancer","volume":"2022","author":"Wang","year":"2022","journal-title":"J. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1093\/jnci\/djp001","article-title":"Lead Time and Overdiagnosis in Prostate-Specific Antigen Screening: Importance of Methods and Context","volume":"101","author":"Draisma","year":"2009","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.mcna.2017.11.001","article-title":"Prostate Cancer Screening","volume":"102","author":"Catalona","year":"2018","journal-title":"Med. Clin. N. Am."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"120","DOI":"10.7326\/0003-4819-157-2-201207170-00459","article-title":"Screening for prostate cancer: U.S. preventive services task force recommendation statement","volume":"157","author":"Moyer","year":"2012","journal-title":"Ann. Intern. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3180","DOI":"10.3934\/mbe.2021158","article-title":"Bioinformatics analysis identified hub genes in prostate cancer tumorigenesis and metastasis","volume":"18","author":"Gu","year":"2021","journal-title":"Math. Biosci. Eng. MBE"},{"key":"ref_15","first-page":"499","article-title":"Characteristic gene expression profiles of benign prostatic hypertrophy and prostate cancer","volume":"35","author":"Endo","year":"2009","journal-title":"Int. J. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sun, J., Li, S., Wang, F., Fan, C., and Wang, J. (2019). Identification of key pathways and genes in pten mutation prostate cancer by bioinformatics analysis. BMC Med. Genet., 20.","DOI":"10.1186\/s12881-019-0923-7"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1186\/s12935-021-02258-3","article-title":"Identification of novel key genes associated with the metastasis of prostate cancer based on bioinformatics prediction and validation","volume":"21","author":"Song","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Liu, K., Chen, Y., Feng, P., Wang, Y., Sun, M., Song, T., Tan, J., Li, C., Liu, S., and Kong, Q. (2022). Identification of Pathologic and Prognostic Genes in Prostate Cancer Based on Database Mining. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.854531"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e13169","DOI":"10.1111\/and.13169","article-title":"Identification of key genes in prostate cancer gene expression profile by bioinformatics","volume":"51","author":"Lu","year":"2019","journal-title":"Andrologia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4736","DOI":"10.18632\/aging.102087","article-title":"Identification of hub genes in prostate cancer using robust rank aggregation and weighted gene co-expression network analysis","volume":"11","author":"Song","year":"2019","journal-title":"Aging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e8786","DOI":"10.7717\/peerj.8786","article-title":"Identification of core genes associated with prostate cancer progression and outcome via bioinformatics analysis in multiple databases","volume":"2020","author":"Wang","year":"2020","journal-title":"PeerJ"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s12935-019-0753-x","article-title":"Combined analysis and validation for DNA methylation and gene expression profiles associated with prostate cancer","volume":"19","author":"Tong","year":"2019","journal-title":"Cancer Cell Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s12253-017-0346-8","article-title":"Integrated Bioinformatics Analysis of Potential Biomarkers for Prostate Cancer","volume":"25","author":"Tan","year":"2017","journal-title":"Pathol. Oncol. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e7872","DOI":"10.7717\/peerj.7872","article-title":"Identification of potential biomarkers and pivotal biological pathways for prostate cancer using bioinformatics analysis methods","volume":"2019","author":"He","year":"2019","journal-title":"PeerJ"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.7150\/jca.29571","article-title":"The Identification of Potential Biomarkers and Biological Pathways in Prostate Cancer","volume":"10","author":"Song","year":"2019","journal-title":"J. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8761112","DOI":"10.1155\/2022\/8761112","article-title":"Identification and Validation of Three Hub Genes Involved in Cell Proliferation and Prognosis of Castration-Resistant Prostate Cancer","volume":"2022","author":"Yu","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"25285","DOI":"10.3390\/ijms161025285","article-title":"Integrated Bioinformatics, environmental epidemiologic and genomic approaches to identify environmental and molecular links between endometriosis and breast cancer","volume":"16","author":"Roy","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_28","unstructured":"Anno, S. (2016). Integrated bioinformatics biostatistics and molecular epidemiologic approaches to study how the environment and genes work together to affect the development of complex chronic diseases. Gene-Environment Interaction Analysis: Methods in Bioinformatics and Computational Biology, Pan Stanford Publishing Pte. Ltd."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1677\/ERC-08-0043","article-title":"Endocrine Disruptors and Prostate Cancer Risk","volume":"15","author":"Prins","year":"2008","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Tarapore, P., Ying, J., Ouyang, B., Burke, B., Bracken, B., and Ho, S.-M. (2014). Exposure to Bisphenol a Correlates with Early-Onset Prostate Cancer and Promotes Centrosome Amplification and Anchorage-Independent Growth in Vitro. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090332"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1080\/10408440490920104","article-title":"A Review of the Endocrine Activity of Parabens and Implications for Potential Risks to Human Health","volume":"35","author":"Golden","year":"2005","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1530\/ERC-16-0175","article-title":"Bisphenol A and Its Analogues Disrupt Centrosome Cycle and Microtubule Dynamics in Prostate Cancer","volume":"24","author":"Ho","year":"2017","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"De Falco, M., and Laforgia, V. (2021). Combined Effects of Different Endocrine-Disrupting Chemicals (EDCs) on Prostate Gland. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18189772"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Alwadi, D., Felty, Q., Roy, D., Yoo, C., and Deoraj, A. (2022). Environmental Phenol and Paraben Exposure Risks and Their Potential Influence on the Gene Expression Involved in the Prognosis of Prostate Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073679"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Alwadi, D., Felty, Q., Yoo, C., Roy, D., and Deoraj, A. (2023). Endocrine Disrupting Chemicals Influence Hub Genes Associated with Aggressive Prostate Cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043191"},{"key":"ref_36","first-page":"1689","article-title":"Induction of Apoptosis in Low to Moderate-Grade Human Prostate Carcinoma by Red Clover-derived Dietary Isoflavones. Cancer Epidemiol","volume":"11","author":"Jarred","year":"2002","journal-title":"Biomark. Prev."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Doultsinos, D., and Mills, I.G. (2021). Derivation and application of molecular signatures to prostate cancer: Opportunities and challenges. Cancers, 13.","DOI":"10.3390\/cancers13030495"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1158\/0008-5472.CAN-07-1246","article-title":"Dietary genistein inhibits metastasis of human prostate cancer in mice","volume":"68","author":"Lakshman","year":"2008","journal-title":"Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.envint.2018.05.052","article-title":"Environmental Phenols and Parabens in Adipose Tissue from Hospitalized Adults in Southern Spain","volume":"119","author":"Frederiksen","year":"2018","journal-title":"Environ. Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3989","DOI":"10.1038\/sj.onc.1210176","article-title":"DNA methylation and histone modification regulate silencing of epithelial cell adhesion molecule for tumor invasion and progression","volume":"26","author":"Tai","year":"2007","journal-title":"Oncogene"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/pros.23446","article-title":"Estrogen receptor signaling in prostate cancer: Implications for carcinogenesis and tumor progression","volume":"78","author":"Bonkhoff","year":"2018","journal-title":"Prostate"},{"key":"ref_42","first-page":"378","article-title":"Expression of P53 and Its Mechanism in Prostate Cancer","volume":"16","author":"Wan","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Habrowska-G\u00f3rczy\u0144ska, D.E., Kozie\u0142, M.J., Kowalska, K., and Piastowska-Ciesielska, A.W. (2021). FOXO3A and Its Regulators in Prostate Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212530"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.ejmech.2018.09.023","article-title":"Computeraided drug discovery of Myc-Max inhibitors as potential therapeutics for prostate cancer","volume":"160","author":"Carabet","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.1038\/s41467-022-30257-z","article-title":"MYC drives aggressive prostate cancer by disrupting transcriptional pause release at androgen receptor targets","volume":"13","author":"Qiu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.canlet.2018.11.019","article-title":"Cyclin B1\/CDK1-regulated mitochondrial bioenergetics in cell cycle progression and tumor resistance","volume":"443","author":"Xie","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Feng, T., Wei, D., Li, Q., Yang, X., Han, Y., Luo, Y., and Jiang, Y. (2021). Four Novel Prognostic Genes Related to Prostate Cancer Identified Using Co-Expression Structure Network Analysis. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.584164"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"627","DOI":"10.21037\/tau-22-281","article-title":"Evaluation of Notch Family Genes\u2019 Expression and Prognostic Value in Prostate Cancer","volume":"11","author":"Qing","year":"2022","journal-title":"Transl. Androl. Urol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1158\/1055-9965.EPI-17-0461","article-title":"Regulatory T-Cell Genes Drive Altered Immune Microenvironment in Adult Solid Cancers and Allow for Immune Contextual Patient Subtyping","volume":"27","author":"Cheng","year":"2018","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1158\/0008-5472.CAN-16-0231","article-title":"P53: Protection against Tumor Growth beyond Effects on Cell Cycle and Apoptosis","volume":"76","author":"Wang","year":"2016","journal-title":"Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zeng, X., Shi, G., He, Q., and Zhu, P. (2021). Screening and Predicted Value of Potential Biomarkers for Breast Cancer Using Bioinformatics Analysis. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-00268-9"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"6240","DOI":"10.18632\/aging.103019","article-title":"Inhibition of Esophageal-Carcinoma Cell Proliferation by Genistein via Suppression of JAK1\/2-STAT3 and AKT\/MDM2\/P53 Signaling Pathways","volume":"12","author":"Gao","year":"2020","journal-title":"Aging"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/cdd.2017.172","article-title":"Cell Cycle Arrest through Indirect Transcriptional Repression by P53: I Have a Dream","volume":"25","author":"Engeland","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/nm.4053","article-title":"Substantial Interindividual and Limited Intraindividual Genomic Diversity among Tumors from Men with Metastatic Prostate Cancer","volume":"22","author":"Kumar","year":"2016","journal-title":"Nat. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3961","DOI":"10.1158\/1078-0432.CCR-05-1977","article-title":"8Q Gain Is an Independent Predictor of Poor Survival in Diagnostic Needle Biopsies from Prostate Cancer Suspects","volume":"12","author":"Ribeiro","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4390","DOI":"10.1158\/0008-5472.CAN-03-3695","article-title":"Genotoxic Stress Induces Expression of E2F4, Leading to Its Association with P130 in Prostate Carcinoma Cells","volume":"64","author":"DuPree","year":"2004","journal-title":"Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1074\/jbc.M005101200","article-title":"p130\/E2F4 binds to and represses the cdc2 promoter in response to p53","volume":"276","author":"Taylor","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5326","DOI":"10.1038\/onc.2008.165","article-title":"RB\/E2F4 and Smad2\/3 Link Survivin to TGF-\u03b2-Induced Apoptosis and Tumor Progression","volume":"27","author":"Yang","year":"2008","journal-title":"Oncogene"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"djw005","DOI":"10.1093\/jnci\/djw005","article-title":"Potential Role for YB-1 in Castration-Resistant Prostate Cancer and Resistance to Enzalutamide through the Androgen Receptor V7","volume":"108","author":"Shiota","year":"2016","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.gene.2012.04.006","article-title":"Functional Coupling of Transcription and Splicing","volume":"501","author":"Montes","year":"2012","journal-title":"Gene"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"878","DOI":"10.15252\/emmm.201303701","article-title":"Targeting the Adaptive Molecular Landscape of Castration-resistant Prostate Cancer","volume":"7","author":"Wyatt","year":"2015","journal-title":"EMBO Mol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"D760","DOI":"10.1093\/nar\/gkl887","article-title":"NCBI GEO: Mining tens of millions of expression profiles\u2014Database and tools update","volume":"35","author":"Barrett","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1530\/ERC-20-0504","article-title":"KLF5 and NFYA Factors as Novel Regulators of Prostate Cancer Cell Metabolism","volume":"28","author":"Poluri","year":"2021","journal-title":"Endocr.-Relat. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"104372","DOI":"10.1016\/j.dib.2019.104372","article-title":"RNA sequencing data of human prostate cancer cells treated with androgens","volume":"25","author":"Poluri","year":"2019","journal-title":"Data Brief"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Jividen, K., Kedzierska, K.Z., Yang, C., Szlachta, K., Ratan, A., and Paschal, B.M. (2018). Genomic analysis of DNA repair genes and androgen signaling in prostate cancer. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4848-x"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1038\/s41467-021-23055-6","article-title":"Androgen signaling uses a writer and a reader of ADP-ribosylation to regulate protein complex assembly","volume":"12","author":"Yang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e129715","DOI":"10.1172\/jci.insight.129715","article-title":"Molecular determinants of response to high-dose androgen therapy in prostate cancer","volume":"4","author":"Nyquist","year":"2019","journal-title":"JCI Insight"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Brzezinka, K., Nevedomskaya, E., Lesche, R., Haegebarth, A., Ter Laak, A., Fern\u00e1ndez-Montalv\u00e1n, A.E., Eberspaecher, U., Werbeck, N.D., Moenning, U., and Siegel, S. (2020). Characterization of the menin-MLL interaction as therapeutic cancer target. Cancers, 12.","DOI":"10.3390\/cancers12010201"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e27159","DOI":"10.7554\/eLife.27159","article-title":"Development of bag-1L as a therapeutic target in androgen receptor-dependent prostate cancer","volume":"6","author":"Cato","year":"2023","journal-title":"eLife"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/nsmb.3153","article-title":"Assembly of methylated KDM1A and CHD1 drives androgen receptor-dependent transcription and translocation","volume":"23","author":"Metzger","year":"2016","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.jnutbio.2008.09.004","article-title":"Profiling of zinc-altered gene expression in human prostate normal vs. cancer cells: A time course study","volume":"20","author":"Lin","year":"2009","journal-title":"J. Nutr. Biochem."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Zhang, H., Gordon, R., Li, W., Yang, X., Pattanayak, A., Fowler, G., Zhang, L., Catalona, W.J., Ding, Y., and Xu, L. (2019). Genistein treatment duration effects biomarkers of cell motility in human prostate. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0214078"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1093\/toxsci\/kfy187","article-title":"Identification of Androgen Receptor Modulators in a Prostate Cancer Cell Line Microarray Compendium","volume":"166","author":"Rooney","year":"2018","journal-title":"Toxicol. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Firlej, V., Soyeux, P., Nourieh, M., Huet, E., Semprez, F., Allory, Y., Londono-Vallejo, A., de la Taille, A., Vacherot, F., and Destouches, D. (2022). Overexpression of Nucleolin and Associated Genes in Prostate Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094491"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1002\/1878-0261.12316","article-title":"Exogenous IL-6 induces mRNA splice variant MBD2_v2 to promote stemness in TP53 wild-type, African American PCa cells","volume":"12","author":"Teslow","year":"2018","journal-title":"Mol. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1038\/s41467-023-37544-3","article-title":"MYC reshapes CTCF-mediated chromatin architecture in prostate cancer","volume":"14","author":"Wei","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Rahman, M.H., Rana, H.K., Peng, S., Hu, X., Chen, C., Quinn, J.M.W., and Moni, M.A. (2021). Bioinformatics and machine learning methodologies to identify the effects of central nervous system disorders on glioblastoma progression. Brief. Bioinform., 22.","DOI":"10.1093\/bib\/bbaa365"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1021\/ci500161d","article-title":"OriginPro 9.1: Scientific data analysis and graphing software-software review","volume":"54","author":"Seifert","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"ref_80","unstructured":"Oliveros, J.C. (2023, November 27). Venny. An Interactive Tool for Comparing Lists with Venn\u2019s Diagrams. (2007\u20132015). Available online: https:\/\/bioinfogp.cnb.csic.es\/tools\/venny\/index.html."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Heberle, H., Meirelles, V.G., da Silva, F.R., Telles, G.P., and Minghim, R. (2015). InteractiVenn: A web-based tool for the analysis of sets through Venn diagrams. BMC Bioinform., 16.","DOI":"10.1186\/s12859-015-0611-3"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1093\/bioinformatics\/btm254","article-title":"GEOquery: A bridge between the Gene Expression Omnibus (GEO) and BioConductor","volume":"23","author":"Davis","year":"2007","journal-title":"Bioinformatics"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/bioinformatics\/btg405","article-title":"Affy\u2014Analysis of Affymetrix GeneChip data at the probe level","volume":"20","author":"Gautier","year":"2004","journal-title":"Bioinformatics"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/bioinformatics\/btn224","article-title":"lumi: A pipeline for processing Illumina microarray","volume":"24","author":"Du","year":"2008","journal-title":"Bioinformatics"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Huang, D.W., Sherman, B.T., Tan, Q., Collins, J.R., Alvord, W.G., Roayaei, J., Stephens, R., Baseler, M.W., Lane, H.C., and Lempicki, R.A. (2007). The DAVID Gene Functional Classification Tool: A novel biological module-centric algorithm to functionally analyze large gene lists. Genome Biol., 8.","DOI":"10.1186\/gb-2007-8-9-r183"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Dennis, G., Sherman, B.T., Hosack, D.A., Yang, J., Gao, W., Lane, H.C., and Lempicki, R.A. (2003). DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol., 4.","DOI":"10.1186\/gb-2003-4-5-p3"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"D545","DOI":"10.1093\/nar\/gkaa970","article-title":"KEGG: Integrating viruses and cellular organisms","volume":"49","author":"Kanehisa","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene Ontology: Tool for the unification of biology","volume":"25","author":"Botstein","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Otasek, D., Morris, J.H., Bou\u00e7as, J., Pico, A.R., and Demchak, B. (2019). Cytoscape Automation: Empowering workflow-based network analysis. Genome Biol., 20.","DOI":"10.1186\/s13059-019-1758-4"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/nmeth.2212","article-title":"A travel guide to Cytoscape plugins","volume":"9","author":"Saito","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software Environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1016\/j.csbj.2022.05.049","article-title":"Computational identification of protein complexes from network interactions: Present state, challenges, and the way forward","volume":"20","author":"Omranian","year":"2022","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/1532-429X-14-83","article-title":"MultiContrast Delayed Enhancement (MCODE) improves detection of subendocardial myocardial infarction by late gadolinium enhancement cardiovascular magnetic resonance: A clinical validation study","volume":"14","author":"Bandettini","year":"2012","journal-title":"J. Cardiovasc. Magn. Reson."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Chin, C., Chen, S., Wu, H., Ho, C., Ko, M., and Lin, C. (2014). CytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC Syst. Biol., 8.","DOI":"10.1186\/1752-0509-8-S4-S11"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"W60","DOI":"10.1093\/nar\/gky311","article-title":"GeneMANIA update 2018","volume":"46","author":"Franz","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1093\/bioinformatics\/btq562","article-title":"GeneMANIA Cytoscape plugin: Fast gene function predictions on the desktop","volume":"26","author":"Montojo","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"W214","DOI":"10.1093\/nar\/gkq537","article-title":"The GeneMANIA prediction server: Biological network integration for gene prioritization and predicting gene function","volume":"38","author":"Donaldson","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Cao, Z., and Zhang, S. (2016). An integrative and comparative study of pan-cancer transcriptomes reveals distinct cancer common and specific signatures. Sci. Rep., 6.","DOI":"10.1038\/srep33398"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio Cancer Genomics Portal: An open platform for exploring multidimensional cancer genomics data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Gu","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/s41587-020-0546-8","article-title":"Visualizing and interpreting cancer genomics data via the Xena platform","volume":"38","author":"Goldman","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"W509","DOI":"10.1093\/nar\/gkaa407","article-title":"TIMER2.0 for analysis of tumor-infiltrating immune cells","volume":"48","author":"Li","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1158\/0008-5472.CAN-17-0307","article-title":"TIMER: A web server for comprehensive analysis of tumor-infiltrating immune cells","volume":"77","author":"Li","year":"2017","journal-title":"Cancer Res."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Li, B., Severson, E., Pignon, J., Zhao, H., Li, T., Novak, J., Jiang, P., Shen, H., Aster, J.C., and Rodig, S. (2016). Comprehensive analyses of tumor immunity: Implications for cancer immunotherapy. Genome Biol., 17.","DOI":"10.1186\/s13059-016-1028-7"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1093\/bioinformatics\/btt019","article-title":"CluePedia Cytoscape plugin: Pathway insights using integrated experimental and in silico data","volume":"29","author":"Bindea","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"IA17","DOI":"10.1158\/1538-7445.CAMODELS2020-IA17","article-title":"Abstract IA17: Defining cancer dependency maps","volume":"80","author":"Hahn","year":"2020","journal-title":"Cancer Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"D1365","DOI":"10.1093\/nar\/gkaa882","article-title":"Project Score database: A resource for investigating cancer cell dependencies and prioritizing therapeutic targets","volume":"49","author":"Dwane","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1136\/archdischild-2016-310459","article-title":"What is CRISPR\/Cas9?","volume":"101","author":"Redman","year":"2016","journal-title":"Arch. Dis. Child. Educ. Pract. Ed."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1128\/MMBR.67.4.657-685.2003","article-title":"RNA Interference: Biology, Mechanism, and Applications","volume":"67","author":"Agrawal","year":"2003","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Chen, E.Y., Tan, C.M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G.V., Clark, N.R., and Ma\u2019ayan, A. (2013). ENRICHR: Interactive and Collaborative HTML5 Gene List Enrichment Analysis Tool. BMC Bioinform., 14.","DOI":"10.1186\/1471-2105-14-128"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: A comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e90","DOI":"10.1002\/cpz1.90","article-title":"Gene Set Knowledge Discovery with ENRICHR","volume":"1","author":"Xie","year":"2021","journal-title":"Curr. Protoc."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Han, H., Shim, H., Shin, D., Shim, J.E., Ko, Y., Shin, J., Kim, H., Cho, A., Kim, E., and Lee, T. (2015). TRRUST: A reference database of human transcriptional regulatory interactions. Sci. Rep., 5.","DOI":"10.1038\/srep11432"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"D380","DOI":"10.1093\/nar\/gkx1013","article-title":"TRRUST v2: An expanded reference database of human and mouse transcriptional regulatory interactions","volume":"46","author":"Han","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1101\/gr.118992.110","article-title":"Prioritizing candidate disease genes by network-based boosting of genome-wide association data","volume":"21","author":"Lee","year":"2011","journal-title":"Genome Res."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Razick, S., Magklaras, G., and Donaldson, I.M. (2008). iRefIndex: A consolidated protein interaction database with provenance. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-405"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1038\/nmeth.3484","article-title":"Phenolyzer: Phenotype-based prioritization of candidate genes for human diseases","volume":"12","author":"Yang","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"D631","DOI":"10.1093\/nar\/gkac883","article-title":"SIGNOR 3.0, the SIGnaling network open resource 3.0: 2022 update","volume":"51","author":"Surdo","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"D548","DOI":"10.1093\/nar\/gkv1048","article-title":"SIGNOR: A database of causal relationships between biological entities","volume":"44","author":"Perfetto","year":"2016","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5463\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:48:03Z","timestamp":1760032083000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,6]]},"references-count":122,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26125463"],"URL":"https:\/\/doi.org\/10.3390\/ijms26125463","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,6,6]]}}}