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

被引：111

作者：

Kneitz, Burkhard ^{[1
]}

Krebs, Markus ^{[1
]}

Kalogirou, Charis ^{[1
]}

Schubert, Maria ^{[1
,5
]}

Joniau, Steven ^{[8
]}

van Poppel, Hein ^{[8
]}

Lerut, Evelyne ^{[9
]}

Kneitz, Susanne ^{[3
]}

Scholz, Claus Juergen ^{[2
]}

Stroebel, Philipp ^{[6
]}

Gessler, Manfred ^{[4
]}

Riedmiller, Hubertus ^{[1
]}

Spahn, Martin ^{[1
,7
]}

机构：

[1] Univ Wurzburg, Univ Hosp Wuerzburg, Dept Urol & Paediat Urol, D-97080 Wurzburg, Germany

[2] Univ Wurzburg, Univ Hosp Wuerzburg, IZKF Lab Microarray Applicat, D-97080 Wurzburg, Germany

[3] Univ Wurzburg, Dept Physiol Chem 1, D-97080 Wurzburg, Germany

[4] Univ Wurzburg, Dept Dev Biochem, Bioctr, D-97080 Wurzburg, Germany

[5] Univ Wurzburg, Comprehens Canc Ctr Mainfranken, D-97080 Wurzburg, Germany

[6] Univ Hosp Gottingen, Dept Pathol, Gottingen, Germany

[7] Univ Hosp Bern, Inselspital, Dept Urol, CH-3010 Bern, Switzerland

[8] Univ Hosp Leuven, Dept Urol, Louvain, Belgium

[9] Univ Hosp Leuven, Dept Pathol, Louvain, Belgium

来源：

CANCER RESEARCH | 2014年 / 74卷 / 09期

关键词：

IFN-GAMMA; RADICAL PROSTATECTOMY; CYTOKINE SIGNALING-3; MICRORNA EXPRESSION; ESOPHAGEAL CANCERS; GROWTH-INHIBITION; STAT3; PROGRESSION; MELANOMA; OVEREXPRESSION;

D O I：

10.1158/0008-5472.CAN-13-1606

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：2591 / 2603

页数：13

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