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.

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 Marchiano, R., A microRNA code for prostate cancer metastasis, <<ONCOGENE>>, 2016; 35 (9): 1180-1192. [doi:10.1038/onc.2015.176] [http://hdl.handle.net/10807/112006]

A microRNA code for prostate cancer metastasis

Coppola, Valeria;Francescangeli, Federica;De Maria Marchiano, Ruggero
2016

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.
2016
Inglese
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 Marchiano, R., A microRNA code for prostate cancer metastasis, <<ONCOGENE>>, 2016; 35 (9): 1180-1192. [doi:10.1038/onc.2015.176] [http://hdl.handle.net/10807/112006]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/112006
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