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Updated: Aug 16, 2026

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
Multi-omics dissection of FOXA1 reveals cancer-type-specific transcriptional networks and functional risk variants
Binjie Luo1,2, Qin Zhang1,3, Xiayun Yang1
1Disease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Aapistie 5A, Oulu 90220, Finland.
Abstract:
FOXA1 is a pioneer transcription factor that shapes lineage-specific regulatory programs in hormone-associated cancers. Here, we integrated FOXA1 cistromes, transcriptomes, GWAS loci, expression-associated quantitative trait loci (eQTL) datasets, clinical cohorts, and functional assays to examine how FOXA1-directed transcriptional networks contribute to prostate and breast cancer biology. We identified high-confidence FOXA1 direct target genes that converge on shared oncogenic pathways while retaining cancer-type-specific regulatory modules. These FOXA1-associated transcriptional programs generated prognostic signatures that stratified patient outcomes across independent cohorts. In prostate cancer, cancer-risk variants were enriched within FOXA1 binding regions, and selected functional variants modulated FOXA1 occupancy and downstream key effector gene (TLE4, USP39, and CPNE1) expression. Functional validation supported roles for these genetically regulated targets in prostate cancer cell proliferation and migration. Together, our findings connect inherited noncoding variation, FOXA1 chromatin binding, transcriptional regulation, and tumor-associated phenotypes, providing a framework for understanding FOXA1-centered regulatory mechanisms in hormone-associated cancers.
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