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

Valentina Doldi, Marzia Pennati, Barbara Forte, Paolo Gandellini, Nadia Zaffaroni (Lead / Corresponding author)

Research output: Contribution to journalReview articlepeer-review

23 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2531-2542
Number of pages12
JournalCellular and Molecular Life Sciences
Volume73
Issue number13
Early online date12 Mar 2016
DOIs
Publication statusPublished - Jul 2016

Keywords

  • Metastasis
  • MicroRNA
  • Prostate cancer
  • Therapeutic targets

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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