Department of Urology and Paediatric Urology, University Hospital Würzburg, Oberdürrbacher Str. 6, Würzburg 97080, Germany.
Int J Mol Sci. 2013 Oct 29;14(11):21414-34. doi: 10.3390/ijms141121414.
The treatment of high-risk prostate cancer (HRPCa) is a tremendous challenge for uro-oncologists. The identification of predictive moleculobiological markers allowing risk assessment of lymph node metastasis and systemic progression is essential in establishing effective treatment. In the current study, we investigate the prognostic potential of miR-205 in HRPCa study and validation cohorts, setting defined clinical endpoints for both. We demonstrate miR-205 to be significantly down-regulated in over 70% of the HRPCa samples analysed and that reconstitution of miR-205 causes inhibition of proliferation and invasiveness in prostate cancer (PCa) cell lines. Additionally, miR-205 is increasingly down-regulated in lymph node metastases compared to the primary tumour indicating that miR-205 plays a role in migration of PCa cells from the original location into extraprostatic tissue. Nevertheless, down-regulation of miR-205 in primary PCa was not correlated to the synchronous presence of metastasis and failed to predict the outcome for HRPCa patients. Moreover, we found a tendency for miR-205 up-regulation to correlate with an adverse outcome of PCa patients suggesting a pivotal role of miR-205 in tumourigenesis. Overall, we showed that miR-205 is involved in the development and metastasis of PCa, but failed to work as a useful clinical biomarker in HRPCa. These findings might have implications for the use of miR-205 as a prognostic or therapeutic target in HRPCa.
高危前列腺癌（HRPCa）的治疗对泌尿肿瘤学家来说是一个巨大的挑战。识别预测性的分子生物学标志物，以评估淋巴结转移和全身进展的风险，对于建立有效的治疗方法至关重要。在本研究中，我们调查了 miR-205 在 HRPCa 研究和验证队列中的预后潜力，为两者都设定了明确的临床终点。我们证明 miR-205 在分析的超过 70%的 HRPCa 样本中显著下调，并且 miR-205 的重建导致前列腺癌细胞系的增殖和侵袭性受到抑制。此外，miR-205 在淋巴结转移中比原发性肿瘤下调得更为明显，这表明 miR-205 在前列腺癌细胞从原始位置迁移到前列腺外组织中发挥作用。然而，miR-205 在原发性前列腺癌中的下调与同步存在转移无关，并且未能预测 HRPCa 患者的预后。此外，我们发现 miR-205 上调与前列腺癌患者的不良预后相关的趋势，表明 miR-205 在肿瘤发生中起着关键作用。总的来说，我们表明 miR-205 参与了前列腺癌的发展和转移，但未能作为 HRPCa 的有用临床生物标志物。这些发现可能对 miR-205 作为 HRPCa 的预后或治疗靶点的应用具有重要意义。
