TY - JOUR
T1 - miR-21
T2 - An androgen receptor-regulated microRNA that promotes hormone-dependent and hormone-independent prostate cancer growth
AU - Ribas, Judit
AU - Ni, Xiaohua
AU - Haffner, Michael
AU - Wentzel, Erik A.
AU - Salmasi, Amirali Hassanzadeh
AU - Chowdhury, Wasim H.
AU - Kudrolli, Tarana A.
AU - Yegnasubramanian, Srinivasan
AU - Luo, Jun
AU - Rodriguez, Ron
AU - Mendell, Joshua T.
AU - Lupold, Shawn E.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-09-1448
DO - 10.1158/0008-5472.CAN-09-1448
M3 - Article
C2 - 19738047
AN - SCOPUS:70349750196
SN - 0008-5472
VL - 69
SP - 7165
EP - 7169
JO - Cancer Research
JF - Cancer Research
IS - 18
ER -