A microRNA code for prostate cancer metastasis

Désirée Bonci, Valeria Coppola, Michele Patrizii, Antonio Addario, A. Cannistraci, Federica Francescangeli, R. Pecci, G. Muto, Devis Collura, R. Bedini, A. Zeuner, Mauro Valtieri, S. Sentinelli, Maria Serena Benassi, Michele Gallucci, Paolo Carlini, Stefano Piccolo, Ruggero Marchiano De Maria

Research output: Contribution to journalArticle

Abstract

Although the development of bone metastasis is a major detrimental event in prostate cancer, the molecular mechanisms responsible for bone homing and destruction remain largely unknown. Here we show that loss of miR-15 and miR-16 in cooperation with increased miR-21 expression promote prostate cancer spreading and bone lesions. This combination of microRNA endows bone-metastatic potential to prostate cancer cells. Concomitant loss of miR-15/miR-16 and gain of miR-21 aberrantly activate TGF-β and Hedgehog signaling, that mediate local invasion, distant bone marrow colonization and osteolysis by prostate cancer cells. These findings establish a new molecular circuitry for prostate cancer metastasis that was validated in patients' cohorts. Our data indicate a network of biomarkers and druggable pathways to improve patient treatment.

Original languageEnglish
Pages (from-to)1180-1192
Number of pages13
JournalOncogene
Volume35
Issue number9
DOIs
Publication statusPublished - Mar 3 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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    Bonci, D., Coppola, V., Patrizii, M., Addario, A., Cannistraci, A., Francescangeli, F., Pecci, R., Muto, G., Collura, D., Bedini, R., Zeuner, A., Valtieri, M., Sentinelli, S., Benassi, M. S., Gallucci, M., Carlini, P., Piccolo, S., & De Maria, R. M. (2016). A microRNA code for prostate cancer metastasis. Oncogene, 35(9), 1180-1192. https://doi.org/10.1038/onc.2015.176