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

2009; American Association for Cancer Research; Volume: 69; Issue: 18 Linguagem: Inglês

10.1158/0008-5472.can-09-1448

1538-7445

Judit Ribas, Xiaohua Ni, Michael C. Haffner, Erik A. Wentzel, Amirali Salmasi, Wasim H. Chowdhury, Tarana A. Kudrolli, Srinivasan Yegnasubramanian, Jun Luo, Ron Rodriguez, Joshua T. Mendell, Shawn E. Lupold,

Cancer-related molecular mechanisms research

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.