Department of experimental Medicine and Biochemical Sciences and Biochemistry Laboratory IDI-IRCCS, University of Rome Tor Vergata, Rome, Italy.
Cell Cycle. 2011 Apr 1;10(7):1121-31. doi: 10.4161/cc.10.7.15180.
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.
前列腺癌从局部病变（原发性肿瘤）缓慢进展为转移性和激素抵抗型表型。在增生的初始步骤之后，在很大比例的病例中发生肿瘤转化事件，较少见的是上皮间质转化和侵袭健康组织（通常是骨骼）。微小 RNA-203（miR-203）是一种肿瘤抑制 microRNA，在不同的恶性肿瘤中经常被沉默。在这里，我们表明 miR-203 在临床原发性前列腺肿瘤中与正常前列腺组织相比下调，并且在转移性前列腺癌细胞系中与正常上皮前列腺细胞相比下调。在脑或骨转移前列腺癌细胞系（DU145 和 PC3）中过表达 miR-203 足以诱导上皮间质转化，同时抑制细胞增殖、迁移和侵袭性。我们已经确定 CKAP2、LASP1、BIRC5、WASF1、ASAP1 和 RUNX2 为涉及这些事件的新的 miR-203 直接靶 mRNA。因此，miR-203 可能是转移性前列腺癌的一个有潜在新的预后标志物和治疗靶点。
