Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the "stemness" marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease.
Deregulation of MIR-34b/Sox2 predicts prostate cancer progression / I. Forno, S. Ferrero, M.V. Russo, G. Gazzano, S. Giangiobbe, E. Montanari, A. Del Nero, B. Rocco, G. Albo, L.R. Languino, D.C. Altieri, V. Vaira, S. Bosari. - In: PLOS ONE. - ISSN 1932-6203. - 10:6(2015 Jun 24), pp. e0130060.1-e0130060.19.
|Titolo:||Deregulation of MIR-34b/Sox2 predicts prostate cancer progression|
|Parole Chiave:||adult; aged; animals; biomarkers, tumor; DNA copy number variations; DNA methylation; disease progression; epigenesis, genetic; gene silencing; humans; male; mice; microRNAs; middle aged; neoplasm recurrence, local; prostate; prostatic neoplasms; SOXB1 transcription factors; signal transduction; stem cells; agricultural and biological sciences (all); biochemistry, genetics and molecular biology (all); medicine (all)|
|Settore Scientifico Disciplinare:||Settore MED/24 - Urologia|
|Data di pubblicazione:||24-giu-2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1371/journal.pone.0130060|
|Appare nelle tipologie:||01 - Articolo su periodico|