title: miR-21: an androgen receptor-regulated microRNA that promotes hormone-dependent and hormone-independent prostate cancer growth.
abstract: 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.
authors.affiliation: The James Buchanan Brady Urological Institute, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Judit
authors.initials: J
authors.lastname: Ribas
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Ni
authors.forename: Michael
authors.initials: M
authors.lastname: Haffner
authors.forename: Erik A
authors.initials: EA
authors.lastname: Wentzel
authors.forename: Amirali Hassanzadeh
authors.initials: AH
authors.lastname: Salmasi
authors.forename: Wasim H
authors.initials: WH
authors.lastname: Chowdhury
authors.forename: Tarana A
authors.initials: TA
authors.lastname: Kudrolli
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Yegnasubramanian
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
authors.forename: Ron
authors.initials: R
authors.lastname: Rodriguez
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Mendell
authors.forename: Shawn E
authors.initials: SE
authors.lastname: Lupold
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics* / Q000378:metabolism; D009919:Orchiectomy; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014183:Transplantation, Heterologous
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D011944:Receptors, Androgen