MicroRNA expression profile of primary prostate cancer stem cells as a source of biomarkers and therapeutic targets

Eur Urol. 2015 Jan;67(1):7-10. doi: 10.1016/j.eururo.2014.09.005. Epub 2014 Sep 16.


MicroRNA (miRNA) expression profiles were generated from prostate epithelial subpopulations 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.

Keywords: Biomarker; Castration-resistant prostate cancer; MicroRNA; Stem cells.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Disease-Free Survival
  • Epithelial Cells
  • Gene Expression Profiling*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Neoplastic Stem Cells*
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Prostatic Hyperplasia / genetics*
  • Prostatic Neoplasms, Castration-Resistant / drug therapy
  • Prostatic Neoplasms, Castration-Resistant / genetics*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Radiation Tolerance / genetics
  • Up-Regulation


  • Biomarkers, Tumor
  • MIRN548 microRNA, human
  • MicroRNAs