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Updated: Sep 26, 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
RNF8 up-regulates AR/ARV7 action to contribute to advanced prostate cancer progression
Tingting Zhou1,2, Shengli Wang1, Xiaoyu Song2
1Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, School of Life Sciences, China Medical University, Shenyang, Liaoning Province, 110122, P. R. China.
Abstract:
Androgen receptor (AR) signaling drives prostate cancer (PC) progression. Androgen deprivation therapy (ADT) is temporally effective, whereas drug resistance inevitably develops. Abnormal expression of AR/ARV7 (the most common AR splicing variant) is critical for endocrine resistance, while the detailed mechanism is still elusive. In this study, bioinformatics and immunohistochemical analyses demonstrate that RNF8 is high expressed in PC and castration-resistant PC (CRPC) samples and the expression of RNF8 is positively correlated with the Gleason score. The high expression of RNF8 in PCs predicts a poor prognosis. These results provide a potential function of RNF8 in PC progression. Furthermore, the mRNA expression of RNF8 is positively correlated with that of AR in PC. Mechanistically, we find that RNF8 upregulates c-Myc-induced AR transcription via altering histone modifications at the c-Myc binding site within the AR gene. RNF8 also acts as a co-activator of AR, promoting the recruitment of AR/ARV7 to the KLK3 (PSA) promoter, where RNF8 modulates histone modifications. These functions of RNF8 are dependent on its E3 ligase activity. RNF8 knockdown further reduces AR transactivation and PSA expression in CRPC cells with enzalutamide treatment. RNF8 depletion restrains cell proliferation and alleviates enzalutamide resistance in CRPC cells. Our findings indicate that RNF8 may be a potential therapeutic target for endocrine resistance in PC.
Insights
RNF8 promotes prostate cancer (PC) progression and endocrine resistance by upregulating androgen receptor (AR) signaling. Targeting RNF8 may offer a new strategy against treatment-resistant prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Androgen receptor (AR) signaling drives prostate cancer (PC) progression.
- Androgen deprivation therapy (ADT) resistance is a major challenge in PC treatment.
- The mechanisms underlying AR and AR variant expression in endocrine resistance are not fully understood.
Purpose of the Study:
- To investigate the role of RNF8 in prostate cancer progression and endocrine resistance.
- To elucidate the mechanism by which RNF8 influences AR signaling.
- To evaluate RNF8 as a potential therapeutic target for castration-resistant PC (CRPC).
Main Methods:
- Bioinformatics and immunohistochemical analyses of PC and CRPC samples.
- Correlation analysis of RNF8 expression with clinical parameters (Gleason score, prognosis).
- Investigation of RNF8's effect on AR transcription, ARV7, c-Myc, and PSA expression in CRPC cells, including assessment of E3 ligase activity and response to enzalutamide treatment.
Main Results:
- RNF8 is highly expressed in PC and CRPC, correlating positively with Gleason score and predicting poor prognosis.
- RNF8 upregulates AR transcription via c-Myc and acts as a co-activator for AR/ARV7 at the PSA promoter, modulating histone modifications.
- RNF8 knockdown reduces AR transactivation and PSA expression, restrains cell proliferation, and alleviates enzalutamide resistance in CRPC cells.
Conclusions:
- RNF8 plays a critical role in promoting PC progression and endocrine resistance.
- RNF8 enhances AR signaling through transcriptional and co-activator mechanisms.
- RNF8 represents a potential therapeutic target for overcoming endocrine resistance in prostate cancer.
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