MiR-203 controls proliferation, migration and invasive potential of prostate cancer cell lines
MiR-203 controls proliferation, migration and invasive potential of prostate cancer cell lines
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DOI：
10.4161/cc.10.7.15180
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发表时间：
2011-04-01
期刊：
影响因子：
4.3
通讯作者：
Melino, Gerry
中科院分区：
文献类型：
--
作者：
Viticchie, Giuditta;Lena, Anna Maria;Melino, Gerry
前列腺癌表现出从局部病变（原发性肿瘤）到转移性和激素抵抗表型的缓慢进展。在增生的初始步骤之后，在很高比例的情况下，会发生肿瘤转化事件，随后是上皮到间质的转变和健康组织（通常是骨骼）的侵袭，但较少发生。 MicroRNA-203 (miR-203) 是一种肿瘤抑制因子 microRNA，在不同的恶性肿瘤中经常被沉默。在这里，我们发现，与正常前列腺组织相比，在临床原发性前列腺肿瘤中，以及与正常上皮前列腺细胞相比，在转移性前列腺癌细胞系中，miR-203 下调。脑或骨转移性前列腺细胞系（DU145 和 PC3）中 miR-203 的过度表达足以诱导间质向上皮细胞的转变，并抑制细胞增殖、迁移和侵袭。我们已确定 CKAP2、LASP1、BIRC5、WASF1、ASAP1 和 RUNX2 是参与这些事件的新 miR-203 直接靶标 mRNA。因此，miR-203可能成为转移性前列腺癌潜在的新预后标志物和治疗靶点。
Prostate cancers show a slow progression from a local lesion (primary tumor) to a metastatic and hormone-resistant phenotype. After an initial step of hyperplasia, in a high percentage of cases a neoplastic transformation event occurs that, less frequently, is followed by epithelial to mesenchymal transition and invasion of healthy tissues (usually bones). MicroRNA-203 (miR-203) is a tumor suppressor microRNA often silenced in different malignancies. Here, we show that miR-203 is downregulated in clinical primary prostatic tumors compared to normal prostate tissue and in metastatic prostate cancer cell lines compared to normal epithelial prostatic cells. Overexpression of miR-203 in brain or bone metastatic prostate cell lines (DU145 and PC3) is sufficient to induce a mesenchymal to epithelial transition with inhibition of cell proliferation, migration and invasiveness. We have identified CKAP2, LASP1, BIRC5, WASF1, ASAP1 and RUNX2 as new miR-203 direct target mRNAs involved in these events. Therefore, miR-203 could be a potentially new prognostic marker and therapeutic target in metastatic prostate cancer.