Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland.
Prostate. 2011 May;71(6):604-14. doi: 10.1002/pros.21276. Epub 2010 Oct 13.
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.
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.
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.
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.
雄激素在雄激素依赖性和去势抵抗性前列腺癌（CRPC）的生长中起着关键作用。只有少数 microRNA（miRNA）被认为受到雄激素的调节。我们旨在确定雄激素调节的 miRNA。
我们利用 LNCaP 衍生的模型，该模型过表达雄激素受体（AR），VCaP 细胞系和 13 对完整去势的前列腺癌（PC）异种移植，以及未经处理的（PC）和 CRPC 的临床标本。通过 microarray 和定量 RT-PCR（Q-RT-PCR）分析 miRNA 的表达。还转染了 pre-miR-141 和 anti-miR-141。
在细胞系中，DHT 处理后有 17 个 miRNA 的表达上调或下调超过 1.5 倍，在 AR 阳性异种移植中，有 42 个 miRNA 在去势后表达上调或下调。只有四个 miRNA（miR-10a、miR-141、miR-150*和 miR-1225-5p）在细胞系和异种移植中表现出相似的雄激素调节。其中，miR-141 在 PC 和 CRPC 中的表达明显高于良性前列腺增生。此外，miR-141 的过表达增强了亲本 LNCaP 细胞的生长，而用 anti-miR-141 抑制 miR-141 的表达则抑制了过表达 AR 的 LNCaP 亚系的生长。
只有少数 miRNA 在细胞系和异种移植模型中被发现受到雄激素的调节。其中，miR-141 在癌症中的表达上调。miR-141 的异位过表达增加了 LNCaP 细胞的生长，表明它可能有助于 PC 的进展。
