Dissecting the role of microRNAs in prostate cancer metastasis: implications for the design of novel therapeutic approaches

TY - JOUR

T1 - Dissecting the role of microRNAs in prostate cancer metastasis

T2 - implications for the design of novel therapeutic approaches

AU - Doldi, Valentina

AU - Pennati, Marzia

AU - Forte, Barbara

AU - Gandellini, Paolo

AU - Zaffaroni, Nadia

N1 - Funding Information: The work in the authors’ laboratory was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC), Projects #11542 (PG) and #12162 (NZ), and the I. Monzino Foundation (NZ). Copyright: © 2016, Springer International Publishing.

PY - 2016/7

Y1 - 2016/7

N2 - Metastatic prostate cancer is a lethal disease that remains incurable despite the recent approval of new drugs, thus making the development of alternative treatment approaches urgently needed. A more precise understanding of the molecular mechanisms underlying prostate cancer dissemination could lead to the identification of novel therapeutic targets for the design of efficient anti-metastatic strategies. MicroRNA (miRNAs) are endogenous, small non-coding RNA molecules acting as key regulators of gene expression at post-transcriptional level. It has been clearly established that altered miRNA expression is a common hallmark of cancer. In addition, emerging evidence suggests their direct involvement in the metastatic cascade. In this review, we present a comprehensive overview of the data generated in experimental tumor models indicating that specific miRNAs may impinge on the different stages of prostate cancer metastasis, including (i) the regulation of epithelial-to-mesenchymal transition and cell migration/invasion, (ii) the interplay between cancer cells and the surrounding stroma, (iii) the control of angiogenesis, (iv) the regulation of anoikis, and (v) the colonization of distant organs. Moreover, we show preliminary evidence of the clinical relevance of some of these miRNAs, in terms of association with tumor aggressiveness/dissemination and clinical outcome, as emerged from translation studies carried out in prostate cancer patient cohorts. We also discuss the potential and the current limitations of manipulating metastasis-related miRNAs, by mimicking or inhibiting them, as a strategy for the development of novel therapeutic approaches for the advanced disease.

AB - Metastatic prostate cancer is a lethal disease that remains incurable despite the recent approval of new drugs, thus making the development of alternative treatment approaches urgently needed. A more precise understanding of the molecular mechanisms underlying prostate cancer dissemination could lead to the identification of novel therapeutic targets for the design of efficient anti-metastatic strategies. MicroRNA (miRNAs) are endogenous, small non-coding RNA molecules acting as key regulators of gene expression at post-transcriptional level. It has been clearly established that altered miRNA expression is a common hallmark of cancer. In addition, emerging evidence suggests their direct involvement in the metastatic cascade. In this review, we present a comprehensive overview of the data generated in experimental tumor models indicating that specific miRNAs may impinge on the different stages of prostate cancer metastasis, including (i) the regulation of epithelial-to-mesenchymal transition and cell migration/invasion, (ii) the interplay between cancer cells and the surrounding stroma, (iii) the control of angiogenesis, (iv) the regulation of anoikis, and (v) the colonization of distant organs. Moreover, we show preliminary evidence of the clinical relevance of some of these miRNAs, in terms of association with tumor aggressiveness/dissemination and clinical outcome, as emerged from translation studies carried out in prostate cancer patient cohorts. We also discuss the potential and the current limitations of manipulating metastasis-related miRNAs, by mimicking or inhibiting them, as a strategy for the development of novel therapeutic approaches for the advanced disease.

KW - Metastasis

KW - MicroRNA

KW - Prostate cancer

KW - Therapeutic targets

UR - https://www.scopus.com/pages/publications/84960398557

U2 - 10.1007/s00018-016-2176-3

DO - 10.1007/s00018-016-2176-3

M3 - Review article

C2 - 26970978

AN - SCOPUS:84960398557

SN - 1420-682X

VL - 73

SP - 2531

EP - 2542

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

IS - 13

ER -