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Updated: Oct 22, 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
Androgens alter the heterogeneity of small extracellular vesicles and the small RNA cargo in prostate cancer
Elena S Martens-Uzunova1, Gina D Kusuma2,3, Stefania Crucitta4
1Department of Urology, Erasmus MC, Cancer Institute University Medical Centre Rotterdam Rotterdam The Netherlands.
Abstract:
Proliferation and survival of prostate cancer cells are driven by the androgen receptor (AR) upon binding to androgen steroid hormones. Manipulating the AR signalling axis is the focus for prostate cancer therapy; thus, it is crucial to understand the role of androgens and AR on extracellular vesicle (EV) secretion and cargo. In this study, we report that plasma-derived circulating vesicles consisting of CD9 and double-positive for CD9 and Prostate Specific Membrane Antigen (PSMA) are increased in patients with advanced metastatic prostate cancer, whereas double positives for CD9 and CD63 small extracellular vesicles (S-EVs) are significantly higher in patients with localised prostate cancer. Androgen manipulation by dihydrotestosterone (DHT) and the clinical antagonist enzalutamide (ENZ) altered the heterogeneity and size of CD9 positive S-EVs in AR expressing prostate cancer cells, while assessment of the total number and protein cargo of total S-EVs was unaltered across different treatment groups. Furthermore, hormone stimulation caused strong and specific effects on the small RNA cargo of S-EVs. A total of 543 small RNAs were found to be regulated by androgens including miR-19-3p and miR-361-5p. Analysis of S-EVs heterogeneity and small RNA cargo may provide clinical utility for prostate cancer and be informative to understand further the mechanism of resistance to androgen targeted therapy in castration-resistant prostate cancer.
Insights
Prostate cancer progression is linked to androgen receptor (AR) signaling. This study reveals that extracellular vesicles (EVs) and their small RNA cargo change with AR activity, offering potential for new diagnostic and therapeutic strategies.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Prostate cancer cell growth relies on the androgen receptor (AR) pathway.
- Understanding androgen's role in extracellular vesicle (EV) secretion is vital for prostate cancer therapy.
- EVs are increasingly recognized as key players in cancer progression and signaling.
Purpose of the Study:
- To investigate the impact of androgens and AR on EV secretion and cargo in prostate cancer.
- To identify specific EV markers associated with different prostate cancer stages.
- To explore how androgen manipulation affects EV heterogeneity and small RNA content.
Main Methods:
- Analysis of plasma-derived circulating vesicles (CD9, CD63, PSMA positive) in prostate cancer patients.
- Treatment of AR-expressing prostate cancer cells with dihydrotestosterone (DHT) and enzalutamide (ENZ).
- Assessment of EV size, heterogeneity, protein, and small RNA cargo using advanced techniques.
Main Results:
- Distinct EV profiles (CD9/PSMA vs. CD9/CD63) correlate with advanced metastatic and localized prostate cancer, respectively.
- Androgen manipulation altered CD9+ S-EV size and heterogeneity but not total protein cargo.
- Hormone stimulation significantly impacted the small RNA cargo of S-EVs, with 543 small RNAs regulated by androgens.
Conclusions:
- EV heterogeneity and small RNA cargo analysis show promise for prostate cancer diagnostics.
- Findings provide insights into the mechanisms of androgen-targeted therapy resistance in castration-resistant prostate cancer.
- Androgen-regulated small RNAs within EVs may serve as biomarkers or therapeutic targets.
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