title: A microRNA code for prostate cancer metastasis.
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.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.|Scientific Directorate, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Bonci
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Coppola
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Patrizii
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Addario
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cannistraci
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Francescangeli
authors.affiliation: Department of Technologies and Health, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Pecci
authors.affiliation: Department of Urology, S Giovanni Bosco Hospital, Turin, Italy.|Department of Urology, Campus Biomedico University, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Muto
authors.affiliation: Department of Urology, S Giovanni Bosco Hospital, Turin, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Collura
authors.affiliation: Department of Technologies and Health, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Bedini
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Zeuner
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Valtieri
authors.affiliation: Scientific Directorate, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Sentinelli
authors.affiliation: Laboratory of Experimental Oncology, Istituti Ortopedici Rizzoli, Bologna, Italy.
authors.forename: M S
authors.initials: MS
authors.lastname: Benassi
authors.affiliation: Scientific Directorate, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Gallucci
authors.affiliation: Scientific Directorate, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Carlini
authors.affiliation: Department of Molecular Medicine, University of Padua School of Medicine, Padua, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Piccolo
authors.affiliation: Scientific Directorate, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: De Maria
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000096:biosynthesis; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D053823:Hedgehog Proteins; C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D016212:Transforming Growth Factor beta