Survival in patients with high-risk prostate cancer is predicted by miR-221, which regulates proliferation, apoptosis, and invasion of prostate cancer cells by inhibiting IRF2 and SOCS3

Cancer Res. 2014 May 1;74(9):2591-603. doi: 10.1158/0008-5472.CAN-13-1606. Epub 2014 Mar 7.


A lack of reliably informative biomarkers to distinguish indolent and lethal prostate cancer is one reason this disease is overtreated. miR-221 has been suggested as a biomarker in high-risk prostate cancer, but there is insufficient evidence of its potential utility. Here we report that miR-221 is an independent predictor for cancer-related death, extending and validating earlier findings. By mechanistic investigations we showed that miR-221 regulates cell growth, invasiveness, and apoptosis in prostate cancer at least partially via STAT1/STAT3-mediated activation of the JAK/STAT signaling pathway. miR-221 directly inhibits the expression of SOCS3 and IRF2, two oncogenes that negatively regulate this signaling pathway. miR-221 expression sensitized prostate cancer cells for IFN-γ-mediated growth inhibition. Our findings suggest that miR-221 offers a novel prognostic biomarker and therapeutic target in high-risk prostate cancer.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interferon Regulatory Factor-2 / genetics*
  • Interferon Regulatory Factor-2 / metabolism
  • Interferon-gamma / physiology
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Phosphorylation
  • Prognosis
  • Proportional Hazards Models
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / mortality
  • Protein Processing, Post-Translational
  • RNA Interference*
  • STAT Transcription Factors / metabolism
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics*
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • Transcriptome


  • IRF2 protein, human
  • Interferon Regulatory Factor-2
  • MIRN221 microRNA, human
  • MicroRNAs
  • SOCS3 protein, human
  • STAT Transcription Factors
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Interferon-gamma