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
2014 | journal article. A publication with affiliation to the University of Göttingen.
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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
Kneitz, B.; Krebs, M.; Kalogirou, C.; Schubert, M.; Joniau, S.; van Poppel, H. & Lerut, E. et al. (2014)
Cancer Research, 74(9) pp. 2591-2603. DOI: https://doi.org/10.1158/0008-5472.CAN-13-1606
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- Authors
- Kneitz, Burkhard; Krebs, Markus; Kalogirou, Charis; Schubert, Maria; Joniau, Steven; van Poppel, Hein; Lerut, Evelyne; Kneitz, Susanne; Scholz, Claus Juergen; Stroebel, Philipp; Gessler, Manfred; Riedmiller, Hubertus; Spahn, Martin
- Abstract
- 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-gamma-mediated growth inhibition. Our findings suggest that miR-221 offers a novel prognostic biomarker and therapeutic target in high-risk prostate cancer. (C) 2014 AACR.
- Issue Date
- 2014
- Status
- published
- Publisher
- Amer Assoc Cancer Research
- Journal
- Cancer Research
- ISSN
- 1538-7445; 0008-5472