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-γ-mediated growth inhibition. Our findings suggest that miR-221 offers a novel prognostic biomarker and therapeutic target in high-risk prostate cancer.
©2014 AACR.
MeSH terms
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Apoptosis
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Cell Line, Tumor
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Cell Proliferation
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Gene Expression
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Gene Expression Regulation, Neoplastic
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Humans
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Interferon Regulatory Factor-2 / genetics*
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Interferon Regulatory Factor-2 / metabolism
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Interferon-gamma / physiology
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Kaplan-Meier Estimate
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Male
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MicroRNAs / genetics*
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Neoplasm Invasiveness
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Phosphorylation
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Prognosis
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Proportional Hazards Models
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Prostatic Neoplasms / genetics
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Prostatic Neoplasms / metabolism*
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Prostatic Neoplasms / mortality
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Protein Processing, Post-Translational
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RNA Interference*
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STAT Transcription Factors / metabolism
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Suppressor of Cytokine Signaling 3 Protein
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Suppressor of Cytokine Signaling Proteins / genetics*
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Suppressor of Cytokine Signaling Proteins / metabolism
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Transcriptome
Substances
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IRF2 protein, human
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Interferon Regulatory Factor-2
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MIRN221 microRNA, human
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MicroRNAs
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SOCS3 protein, human
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STAT Transcription Factors
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Suppressor of Cytokine Signaling 3 Protein
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Suppressor of Cytokine Signaling Proteins
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Interferon-gamma