| First Author | Forno I | Year | 2015 |
| Journal | PLoS One | Volume | 10 |
| Issue | 6 | Pages | e0130060 |
| PubMed ID | 26107383 | Mgi Jnum | J:233799 |
| Mgi Id | MGI:5788072 | Doi | 10.1371/journal.pone.0130060 |
| Citation | Forno I, et al. (2015) Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression. PLoS One 10(6):e0130060 |
| abstractText | 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. |
