Androgen regulation of micro-RNAs in prostate cancer.

Autor: Waltering KK; Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland., Porkka KP, Jalava SE, Urbanucci A, Kohonen PJ, Latonen LM, Kallioniemi OP, Jenster G, Visakorpi T
Jazyk: angličtina
Zdroj: The Prostate [Prostate] 2011 May; Vol. 71 (6), pp. 604-14. Date of Electronic Publication: 2010 Oct 13.
DOI: 10.1002/pros.21276
Abstrakt: Background: Androgens play a critical role in the growth of both androgen dependent and castration-resistant prostate cancer (CRPC). Only a few micro-RNAs (miRNAs) have been suggested to be androgen regulated. We aim to identify androgen regulated miRNAs.
Methods: We utilized LNCaP derived model, we have established, and which overexpresses the androgen receptor (AR), the VCaP cell line, and 13 intact-castrated prostate cancer (PC) xenograft pairs, as well as clinical specimens of untreated (PC) and CRPC. The expression of miRNAs was analyzed by microarrays and quantitative RT-PCR (Q-RT-PCR). Transfection of pre-miR-141 and anti-miR-141 was also used.
Results: Seventeen miRNAs were > 1.5-fold up- or downregulated upon dihydrotestosterone (DHT) treatment in the cell lines, and 42 after castration in the AR-positive xenografts. Only four miRNAs (miR-10a, miR-141, miR-150*, and miR-1225-5p) showed similar androgen regulation in both cell lines and xenografts. Of those, miR-141 was found to be expressed more in PC and CRPC compared to benign prostate hyperplasia. Additionally, the overexpression of miR-141 enhanced growth of parental LNCaP cells while inhibition of miR-141 by anti-miR-141 suppressed the growth of the LNCaP subline overexpressing AR.
Conclusions: Only a few miRNAs were found to be androgen-regulated in both cell lines and xenografts models. Of those, the expression of miR-141 was upregulated in cancer. The ectopic overexpression of miR-141 increased growth of LNCaP cell suggesting it may contribute to the progression of PC.
(Copyright © 2010 Wiley-Liss, Inc.)
Databáze: MEDLINE
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