miR-21: an androgen receptor-regulated microRNA that promotes hormone-dependent and hormone-independent prostate cancer growth.
Cancer Res, 2009/9/15;69(18):7165-9.
Ribas J[1], Ni X, Haffner M, Wentzel EA, Salmasi AH, Chowdhury WH, Kudrolli TA, Yegnasubramanian S, Luo J, Rodriguez R, Mendell JT, Lupold SE
Affiliations
PMID: 19738047DOI: 10.1158/0008-5472.CAN-09-1448
Impact factor: 13.312
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.
MeSH terms
Animals; Cell Growth Processes; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Mice, Nude; MicroRNAs; Neoplasms, Hormone-Dependent; Orchiectomy; Promoter Regions, Genetic; Prostatic Neoplasms; Receptors, Androgen; Transfection; Transplantation, Heterologous
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