外泌體 miR-10a-3p 抑制去勢抗性攝護腺癌中的雄性素受體訊號傳導

Exosomal miR-10a-3p Suppresses Androgen Receptor Signaling in Castration-Resistant Prostate Cancer

柳瑞明^1,2、許仁駿^3,4、Ainani Priza Minhalina⁵、崔克宏^6,7、劉兆蓮^5,8

Jui-Ming Liu^1,2, Ren-Jun Hsu^3,4 Ainani Priza Minhalina⁵, Ke-Hung Tsui^6,7, Chao Lien Liu^5,8

1.衛生福利部桃園醫院 泌尿科

2.國防醫學大學 三軍總醫院 婦產部

3.佛教慈濟醫療財團法人花蓮慈濟醫院 癌症研究中心

4.慈濟大學 醫學院

5.臺北醫學大學 醫學科技學院 醫學檢驗暨生物技術學系

6.臺北醫學大學 泌尿學科

7.臺北醫學大學 萬芳醫院 泌尿科

8.臺北醫學大學 醫學科技學院 醫學生物技術博士班

¹. Department of Urology , Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan

²  Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

³.Cancer Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

⁴. College of medicine, Tzu Chi University, Hualien, Taiwan

⁵. School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.

⁶. Department of Urology, Taipei Medical University, Taipei, Taiwan

⁷. Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.

⁸. PhD program in Medical Biotechnology, College of medical Science and Technology, Taipei Medical University, Taipei , Taiwan

Introduction: Prostate cancer (PC) is the most common malignancy among men and the second leading cause of cancer-related mortality worldwide. Although androgen deprivation therapy (ADT) is initially effective, resistance typically develops within 2–3 years, leading to castration-resistant prostate cancer (CRPC). Current therapies¾including next-generation anti-androgens, radiopharmaceuticals, PARP inhibitors, and taxane-based chemotherapies¾ offer limited benefit, underscoring the need for novel therapeutic strategies.  

Materials and Methods: To investigate the role of exosomal miR-10a-3p in CRPC progression, 22RV1 and DU145 cells were transduced with lentivirus to overexpress miR-10a-3p. Functional assays evaluated proliferation, invasion, and T cell recruitment. In vivo, miR-10a-3p-overexpressing 22RV1 cells were implanted into immunodeficient mice to assess tumorigenesis. Transcriptomic changes were analyzed by mRNA sequencing.

Results: Lentiviral transduction significantly increased miR-10a-3p expression in both cell lines (22RV1, ***p < 0.001; DU145, **p < 0.01). Overexpression reduced proliferation in 22RV1 cells (**p < 0.01) and significantly downregulated AR-FL (**p < 0.01) and AR-V7 (****p < 0.0001). Both cell lines exhibited decreased invasion (22RV1, ***p < 0.001; DU145, ****p < 0.0001) and enhanced recruitment of activated T cells (22RV1, ***p < 0.001; DU145, **p < 0.01). In vivo, miR-10a-3p overexpression suppressed tumor growth compared to controls (**p < 0.01). Mechanistically, miR-10a-3p targeted AR coactivators (AIB1 and SRC-1), reducing AR activity and PSA expression, thereby limiting cell growth and therapy resistance.

Conclusions: Exosomal miR-10a-3p acts as a potent suppressor of androgen receptor signaling, inhibiting CRPC cell growth and invasion both in vitro and in vivo. These findings identify miR-10a-3p as a promising therapeutic candidate for overcoming resistance and improving outcomes in CRPC.