title: 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.
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.
authors.affiliation: Authors' Affiliations: Department of Urology and Paediatric Urology, University Hospital Wuerzburg; IZKF Laboratory for Microarray Applications, University Hospital Wuerzburg; Departments of Physiological Chemistry I; Developmental Biochemistry, Biocenter; Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Wuerzburg; Department of Pathology, University Hospital Goettingen, Goettingen, Germany; Department of Urology, University Hospital Bern, Inselspital, Bern, Switzerland; and Departments of Urology and Pathology, University Hospital Leuven, Leuven, Belgium.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Kneitz
authors.forename: Markus
authors.initials: M
authors.lastname: Krebs
authors.forename: Charis
authors.initials: C
authors.lastname: Kalogirou
authors.forename: Maria
authors.initials: M
authors.lastname: Schubert
authors.forename: Steven
authors.initials: S
authors.lastname: Joniau
authors.forename: Hein
authors.initials: H
authors.lastname: van Poppel
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lerut
authors.forename: Susanne
authors.initials: S
authors.lastname: Kneitz
authors.forename: Claus Jürgen
authors.initials: CJ
authors.lastname: Scholz
authors.forename: Philipp
authors.initials: P
authors.lastname: Ströbel
authors.forename: Manfred
authors.initials: M
authors.lastname: Gessler
authors.forename: Hubertus
authors.initials: H
authors.lastname: Riedmiller
authors.forename: Martin
authors.initials: M
authors.lastname: Spahn
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050836:Interferon Regulatory Factor-2 / Q000235:genetics* / Q000378:metabolism; D007371:Interferon-gamma / Q000502:physiology; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D050791:STAT Transcription Factors / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome
chemical_list: D050836:Interferon Regulatory Factor-2; D007371:Interferon-gamma; D035683:MicroRNAs; D050791:STAT Transcription Factors; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C494229:IRF2 protein, human; C525709:MIR221, human; C106644:SOCS3 protein, human