miR-21: An Androgen Receptor-Regulated MicroRNA that Promotes Hormone-Dependent and Hormone-Independent Prostate Cancer Growth

• Published in: Cancer research (Chicago, Ill.) Vol. 69; no. 18; pp. 7165 - 7169
• Main Authors: RIBAS, Judit, XIAOHUA NI, MENDELL, Joshua T, LUPOLD, Shawn E, HAFFNER, Michael, WENTZEL, Erik A, HASSANZADEH SALMASI, Amirali, CHOWDHURY, Wasim H, KUDROLLI, Tarana A, YEGNASUBRAMANIAN, Srinivasan, LUDO, Jun, RODRIGUEZ, Ron
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-09-2009
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Cell Growth Processes - physiology; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Mice; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; Neoplasms, Hormone-Dependent - genetics; Neoplasms, Hormone-Dependent - metabolism; Nephrology. Urinary tract diseases; Orchiectomy; Pharmacology. Drug treatments; Promoter Regions, Genetic; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Receptors, Androgen - genetics; Receptors, Androgen - metabolism; Transfection; Transplantation, Heterologous; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Hormonodependence; Urinary system disease; RNA interference; Prostate disease; Growth; Micro RNA; Malignant tumor; Gene silencing; Androgen receptor; Male genital diseases; Prostate cancer; Cancer; Hormonal receptor
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-09-1448

Androgen receptor (AR)-mediated oncogenic pathways have not been fully elucidated. In this study, we used high-throughput microarray analysis on two AR-positive prostate cancer (CaP) cell lines to identify 16 AR-responsive microRNAs (miRNA). We focused on miR-21 because of its previously reported oncogenic activity in other cancers. We show androgen-induced AR binding to the defined miR-21 promoter, miPPR-21, suggesting direct transcriptional regulation. Inhibition of miR-21 diminished androgen-induced CaP cell proliferation, providing new evidence that miRNAs can contribute to androgen-driven cell growth. Elevated expression of miR-21 enhanced CaP tumor growth in vivo and, surprisingly, was sufficient for androgen-dependent tumors to overcome castration-mediated growth arrest. Thus, elevated miR-21 expression alone is sufficient to impart castration resistance. Moreover, quantitative reverse transcription-PCR analysis revealed elevated miR-21 expression in CaP when compared with adjacent normal tissue. These results suggest that miR-21 may contribute to CaP pathogenesis.