A basal-enriched microRNA is required for prostate tumorigenesis in a Pten knockout mouse model

在Pten基因敲除小鼠模型中,一种富集于基底细胞的microRNA是前列腺肿瘤发生所必需的。

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Abstract

MicroRNAs (miRNAs) play important roles in prostate cancer development. However, it remains unclear how individual miRNAs contribute to the initiation and progression of prostate cancer. Here we show that a basal layer-enriched miRNA is required for prostate tumorigenesis. We identify miR-205 as the most highly expressed miRNA and enriched in the basal cells of the prostate. Although miR-205 is not required for normal prostate development and homeostasis, genetic deletion of miR-205 in a Pten null tumor model significantly compromises tumor progression and does not promote metastasis. In Pten null basal cells, loss of miR-205 attenuates pAkt levels and promotes cellular senescence. Furthermore, although overexpression of miR-205 in prostate cancer cells with luminal phenotypes inhibits cell growth in both human and mouse, miR-205 has a minimal effect on the growth of a normal human prostate cell line. Taken together, we have provided genetic evidence for a requirement of miR-205 in the progression of Pten null-induced prostate cancer.

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