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J Biol Chem ; 287(2): 1527-37, 2012 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-22128178

RESUMEN

Castration-resistant prostate cancer continues to rely on androgen receptor (AR) expression. AR plays a central role in the development of prostate cancer and progression to castration resistance during and after androgen deprivation therapy. Here, we identified miR-let-7c as a key regulator of expression of AR. miR-let-7c suppresses AR expression and activity in human prostate cancer cells by targeting its transcription via c-Myc. Suppression of AR by let-7c leads to decreased cell proliferation of human prostate cancer cells. Down-regulation of Let-7c in prostate cancer specimens is inversely correlated with AR expression, whereas the expression of Lin28 (a repressor of let-7) is correlated positively with AR expression. Our study demonstrates that the miRNA let-7c plays an important role in the regulation of androgen signaling in prostate cancer by down-regulating AR expression. These results suggest that reconstitution of miR-let-7c may aid in targeting enhanced and hypersensitive AR in advanced prostate cancer.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , MicroARNs/biosíntesis , Neoplasias de la Próstata/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , ARN Neoplásico/biosíntesis , Receptores Androgénicos/biosíntesis , Línea Celular Tumoral , Proliferación Celular , Humanos , Masculino , MicroARNs/genética , Neoplasias de la Próstata/genética , Proteínas Proto-Oncogénicas c-myc/genética , ARN Neoplásico/genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Receptores Androgénicos/genética , Transducción de Señal/genética
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