Weidle Ulrich H, Epp Alexandra, Birzele Fabian, Brinkmann Ulrich
Roche Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany
Roche Pharma Research and Early Development, Roche Innovation Center Munich, Penzberg, Germany.
Cancer Genomics Proteomics. 2019 Jan-Feb;16(1):1-19. doi: 10.21873/cgp.20108.
The mortality of patients with hormone-resistant prostate cancer can be ascribed to a large degree to metastasis to distant organs, predominantly to the bones. In this review, we discuss the contribution of micro-RNAs (miRs) to the metastatic process of prostate cancer. The criteria for selection of miRs for this review were the availability of preclinical in vivo metastasis-related data in conjunction with prognostic clinical data. Depending on their function in the metastatic process, the corresponding miRs are up- or down-regulated in prostate cancer tissues when compared to matching normal tissues. Up-regulated miRs preferentially target suppressors of cytokine signaling or tumor suppressor-related genes and metastasis-inhibitory transcription factors. Down-regulated miRs promote epithelial-mesenchymal transition or mesenchymal-epithelial transition and diverse pro-metastatic signaling pathways. Some of the discussed miRs exert their function by simultaneously targeting epigenetic pathways as well as cell-cycle-related, anti-apoptotic and signaling-promoting targets. Finally, we discuss potential therapeutic options for the treatment of prostate cancer-related metastases by substitution or inhibition of miRs.
激素抵抗性前列腺癌患者的死亡率在很大程度上可归因于远处器官转移,主要是骨转移。在本综述中,我们讨论了微小RNA(miR)在前列腺癌转移过程中的作用。本综述中miR的选择标准是要有临床前体内转移相关数据以及预后临床数据。根据其在转移过程中的功能,与匹配的正常组织相比,相应的miR在前列腺癌组织中上调或下调。上调的miR优先靶向细胞因子信号转导抑制因子或肿瘤抑制相关基因以及转移抑制转录因子。下调的miR促进上皮-间质转化或间质-上皮转化以及多种促转移信号通路。一些讨论的miR通过同时靶向表观遗传途径以及细胞周期相关、抗凋亡和信号促进靶点发挥其功能。最后,我们讨论了通过替代或抑制miR治疗前列腺癌相关转移的潜在治疗选择。