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Updated: Sep 19, 2025

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
A Super-Enhancer-Driven Transcriptional Regulatory Circuit Underlying Abiraterone Resistance in Castration-Resistant
Liling Jiang1,2, Jiamin Wang3, Guanjie Peng1,4
1Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, 511436, P. R. China.
None:
Castration-resistant prostate cancer (CRPC) remains the leading cause of mortality among prostate cancer patients. While second-generation androgen receptor (AR) pathway-targeted therapies, such as Abiraterone, have significantly improved survival outcomes, resistance to these treatments ultimately emerges, posing a critical challenge. Understanding the mechanisms underlying Abiraterone resistance is essential for developing strategies to enhance patient outcomes. In this study, a super-enhancer (SE)-driven transcriptional regulatory circuit is identified involving BCL6, NFIB, and SMAD3 that facilitates Abiraterone resistance in CRPC. Through comprehensive analyses of SE expression profiles in Abiraterone-resistant CRPC cells and their parental counterparts, it is revealed that this circuit plays a pivotal role in resistance progression. Mechanistically, BCL6, NFIB, and SMAD3 synergistically remodel the transcriptional landscape of resistant CRPC cells, driving resistance by regulating cholesterol biosynthesis and cell cycle pathways. The findings provide critical insights into the transcriptional dysregulation underlying Abiraterone resistance and highlight potential therapeutic strategies to counteract treatment resistance in CRPC, ultimately aiming to improve patient survival and quality of life.
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