Journal
EUROPEAN UROLOGY
Volume 67, Issue 1, Pages 7-10Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.eururo.2014.09.005
Keywords
MicroRNA; Stem cells; Biomarker; Castration-resistant prostate cancer
Categories
Funding
- PRO-NEST Marie-Curie Grant
- Finnish Funding Agency for Technology and Innovation Finland Distinguished Professor programme
- Academy of Finland [132877]
- Yorkshire Cancer Research
- Cancer Foundation Finland sr [130133] Funding Source: researchfish
- Academy of Finland (AKA) [132877, 132877] Funding Source: Academy of Finland (AKA)
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MicroRNA (miRNA) expression profiles were generated from prostate epithelial sub-populations enriched from patient-derived benign prostatic hyperplasia (n = 5), Gleason 7 treatment-naive prostate cancer (PCa) (n = 5), and castration-resistant PCa (CRPC) (n = 3). Microarray expression was validated in an independent patient cohort (n = 10). Principal component analysis showed that miRNA expression is clustered by epithelial cell phenotype, regardless of pathologic status. We also discovered concordance between the miRNA expression profiles of unfractionated epithelial cells from CRPCs, human embryonic stem cells (SCs), and prostate epithelial SCs (both benign and malignant). MiR-548c-3p was chosen as a candidate miRNA from this group to explore its usefulness as a CRPC biomarker and/or therapeutic target. Overexpression of miR-548c-3p was confirmed in SCs (fivefold, p < 0.05) and in unfractionated CRPCs (1.8-fold, p < 0.05). Enforced overexpression of miR-548c-3p in differentiated cells induced stemlike properties (p < 0.01) and radioresistance (p < 0.01). Reanalyses of published studies further revealed that miR-548c-3p is significantly overexpressed in CRPC (p < 0.05) and is associated with poor recurrence-free survival (p < 0.05), suggesting that miR-548c-3p is a functional biomarker for PCa aggressiveness. Our results validate the prognostic and therapeutic relevance of miRNAs for PCa management while demonstrating that resolving cell-type and differentiation-specific differences is essential to obtain clinically relevant miRNA expression profiles. Patient summary: We report microRNA (miRNA) expression profiles of epithelial cell fractions from the human prostate, including stem cells. miR-548c-3p was revealed as a functional biomarker for prostate cancer progression. The evaluation of miR-548c-3p in a larger patient cohort should yield information on its clinical usefulness. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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