A microRNA code for prostate cancer metastasis

Ruggero De Maria Marchiano, Valeria Coppola, Federica Francescangeli, D. Bonci, V. Coppola, M. Patrizii, A. Addario, A. Cannistraci, F. Francescangeli, R. Pecci, G. Muto, D. Collura, R. Bedini, A. Zeuner, M. Valtieri, S. Sentinelli, M. S. Benassi, M. Gallucci, P. Carlini, S. Piccolo

Risultato della ricerca: Contributo in rivistaArticolo in rivista

88 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)1180-1192
Numero di pagine13
RivistaOncogene
Volume35
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • Animals
  • Biomarkers, Tumor
  • Bone Neoplasms
  • Cancer Research
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic
  • Genetics
  • Hedgehog Proteins
  • Humans
  • Male
  • MicroRNAs
  • Molecular Biology
  • Neoplasm Invasiveness
  • Prostatic Neoplasms
  • Signal Transduction
  • Transforming Growth Factor beta

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