The Prostate 71:604 ^ 614 (2011) Androgen Regulation of micro-RNAs in Prostate Cancer Kati K. Waltering, 1 Kati P. Porkka, 1 Sanni E. Jalava, 1 Alfonso Urbanucci, 1 Pekka J. Kohonen, 2 Leena M. Latonen, 1 Olli P. Kallioniemi, 2,3 Guido Jenster, 4 and Tapio Visakorpi 1 * 1 Institute of Medical Technology,University of Tampere and Tampere University Hospital,Tampere, Finland 2 Medical Biotechnology,VTT Technical Research Centre of Finland,Turku, Finland 3 Institute for Molecular Medicine Finland (FIMM),University of Helsinki, Helsinki, Finland 4 Department of Urology, Josephine Nefkens Institute, Erasmus University Medical Center, Rotterdam,The Netherlands BACKGROUND. Androgens play a critical role in the growth of both androgen dependent and castration-resistant prostate cancer (CRPC). Only a few micro-RNAs (miRNAs) have been suggested to be androgen regulated. We aim to identify androgen regulated miRNAs. METHODS. We utilized LNCaP derived model, we have established, and which over- expresses the androgen receptor (AR), the VCaP cell line, and 13 intact-castrated prostate cancer (PC) xenograft pairs, as well as clinical specimens of untreated (PC) and CRPC. The expression of miRNAs was analyzed by microarrays and quantitative RT-PCR (Q-RT-PCR). Transfection of pre-miR-141 and anti-miR-141 was also used. RESULTS. Seventeen miRNAs were >1.5-fold up- or downregulated upon dihydrotestoster- one (DHT) treatment in the cell lines, and 42 after castration in the AR-positive xenografts. Only four miRNAs (miR-10a, miR-141, miR-150*, and miR-1225-5p) showed similar androgen regulation in both cell lines and xenografts. Of those, miR-141 was found to be expressed more in PC and CRPC compared to benign prostate hyperplasia. Additionally, the overexpression of miR-141 enhanced growth of parental LNCaP cells while inhibition of miR-141 by anti-miR-141 suppressed the growth of the LNCaP subline overexpressing AR. CONCLUSIONS. Only a few miRNAs were found to be androgen-regulated in both cell lines and xenografts models. Of those, the expression of miR-141 was upregulated in cancer. The ectopic overexpression of miR-141 increased growth of LNCaP cell suggesting it may contribute to the progression of PC. Prostate 71: 604–614, 2011. # 2010 Wiley-Liss, Inc. KEY WORDS: AR; prostatic carcinoma; neoplasia; hormone-refractory; LNCaP-ARhi INTRODUCTION The development and growth of prostate cancer (PC) is dependent on androgens. Thus the standard treatment for advanced PC has, for the past half- century, been androgen deprivation [1]. Although initially almost all tumors respond to androgen deprivation therapy, this treatment ultimately fails due to the emergence of castration-resistant prostate cancer (CRPC). It was previously believed that CRPC cells are truly androgen independent, however it has now been shown that CRPC cell are androgen sensitive—even hypersensitive [2–4]. In normal pros- Grant sponsor: European Community’s Seventh Framework Programme; Grant numbers: FP7/2007-2013, HEALTH-F2-2007- 201438; Grant sponsor: Academy of Finland; Grant sponsor: Cancer Society of Finland; Grant sponsor: Reino Lahtikari Foundation; Grant sponsor: Sigrid Juselius Foundation; Grant sponsor: Medical Research Fund of Tampere University Hospital; Grant sponsor: Finnish Cultural Foundation; Grant sponsor: University of Tampere Foundation. *Correspondence to: Tapio Visakorpi, MD, PhD, Institute of Medical Technology, University of Tampere, FIN-33014 Tampere, Finland. E-mail: tapio.visakorpi@uta.fi Received 28 May 2010; Accepted 24 August 2010 DOI 10.1002/pros.21276 Published online 14 October 2010 in Wiley Online Library (wileyonlinelibrary.com). ß 2010 Wiley-Liss, Inc.