The Functional Role of Prostate Cancer Metastasis-related Micro-RNAs

Abstract

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.

Keywords: In vivo metastasis models; interference with signaling networks; miR substitution and inhibition; pro-metastatic pathways; prognostic aspects; review; target validation.