Loss of expression of context-specific tumor suppressors is a critical event that facilitates the development of prostate cancer. Zinc finger and BTB domain containing transcriptional repressors, such as ZBTB7A and ZBTB16, have been recently identified as tumor suppressors that play important roles in preventing prostate cancer progression. In this study, we used combined ChIP-seq and RNA-seq analyses of prostate cancer cells to identify direct ZBTB7A-repressed genes, which are enriched for transcriptional targets of E2F, and identified that the androgen receptor (AR) played a critical role in the transcriptional suppression of these E2F targets. AR recruitment of the retinoblastoma protein (Rb) was required to strengthen the E2F-Rb transcriptional repression complex. In addition, ZBTB7A was rapidly recruited to the E2F-Rb binding sites by AR and negatively regulated the transcriptional activity of E2F1 on DNA replication genes. Finally, ZBTB7A suppressed the growth of castration-resistant prostate cancer (CRPC) and , and overexpression of ZBTB7A acted in synergy with high-dose testosterone treatment to effectively prevent the recurrence of CRPC. Overall, this study provides novel molecular insights of the role of ZBTB7A in CRPC cells and demonstrates globally its critical role in mediating the transcriptional repression activity of AR. SIGNIFICANCE: ZBTB7A is recruited to the E2F-Rb binding sites by AR and negatively regulates the transcriptional activity of E2F1 on DNA replication genes.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801099 | PMC |
http://dx.doi.org/10.1158/0008-5472.CAN-19-0815 | DOI Listing |
Ann Nucl Med
January 2025
Department of Biomedical Sciences, Humanitas University, Milan, Italy.
The purpose of this systematic review was to evaluate the role of PSMA PET/CT in intermediate-risk prostate cancer (PCa) patients, to determine whether it could help improve treatment strategy and prognostic stratification. A systematic literature search up to May 2024 was conducted in the PubMed, Embase and Scopus databases. Articles with mixed risk patient populations, review articles, editorials, letters, comments, or case reports were excluded.
View Article and Find Full Text PDFJ Neurooncol
January 2025
Department of Neurosurgery, Allegheny Health Network, Neuroscience Institute, Pittsburgh, PA, United States.
Langenbecks Arch Surg
January 2025
Department for the Promotion of Medical Device Innovation, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Purpose: Assessing surgical skills is vital for training surgeons, but creating objective, automated evaluation systems is challenging, especially in robotic surgery. Surgical procedures generally involve dissection and exposure (D/E), and their duration and proportion can be used for skill assessment. This study aimed to develop an AI model to acquire D/E parameters in robot-assisted radical prostatectomy (RARP) and verify if these parameters could distinguish between novice and expert surgeons.
View Article and Find Full Text PDFInsights Imaging
January 2025
Department of Radiology, the Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China.
Objective: To evaluate the feasibility of utilizing artificial intelligence (AI)-predicted biparametric MRI (bpMRI) image features for predicting the aggressiveness of prostate cancer (PCa).
Materials And Methods: A total of 878 PCa patients from 4 hospitals were retrospectively collected, all of whom had pathological results after radical prostatectomy (RP). A pre-trained AI algorithm was used to select suspected PCa lesions and extract lesion features for model development.
Mov Disord Clin Pract
January 2025
The Edmond J. Safra Program in Parkinson's Disease, University Health Network and the University of Toronto, Toronto, Ontario, Canada.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!