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Br J Cancer. 2015 Sep 29;113(7):1055-65. doi: 10.1038/bjc.2015.300. Epub 2015 Sep 1.

MicroRNA expression signature of castration-resistant prostate cancer: the microRNA-221/222 cluster functions as a tumour suppressor and disease progression marker.

Author information

1
Department of Functional Genomics, Chiba University Graduate School of Medicine, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
2
Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
3
Department of Urology, Teikyo University Chiba Medical Centre, Chiba, Japan.
4
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
5
Department of Pathology, Teikyo University Chiba Medical Centre, Chiba, Japan.

Abstract

BACKGROUND:

Our present study of the microRNA (miRNA) expression signature in castration-resistant prostate cancer (CRPC) revealed that the clustered miRNAs microRNA-221 (miR-221) and microRNA-222 (miR-222) are significantly downregulated in cancer tissues. The aim of this study was to investigate the functional roles of miR-221 and miR-222 in prostate cancer (PCa) cells.

METHODS:

A CRPC miRNA signature was constructed by PCR-based array methods. Functional studies of differentially expressed miRNAs were analysed using PCa cells. The association between miRNA expression and overall survival was estimated by the Kaplan-Meier method. In silico database and genome-wide gene expression analyses were performed to identify molecular targets regulated by the miR-221/222 cluster.

RESULTS:

miR-221 and miR-222 were significantly downregulated in PCa and CRPC specimens. Kaplan-Meier survival curves showed that low expression of miR-222 predicted a short duration of progression to CRPC. Restoration of miR-221 or miR-222 in cancer cells revealed that both miRNAs significantly inhibited cancer cell migration and invasion. Ecm29 was directly regulated by the miR-221/222 cluster in PCa cells.

CONCLUSIONS:

Loss of the tumour-suppressive miR-221/222 cluster enhanced migration and invasion in PCa cells. Our data describing targets regulated by the tumour-suppressive miR-221/222 cluster provide insights into the mechanisms of PCa and CRPC progression.

PMID:
26325107
PMCID:
PMC4651127
DOI:
10.1038/bjc.2015.300
[Indexed for MEDLINE]
Free PMC Article

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