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Br J Cancer. 2016 May 10;114(10):1135-44. doi: 10.1038/bjc.2016.95. Epub 2016 Apr 12.

Regulation of E3 ubiquitin ligase-1 (WWP1) by microRNA-452 inhibits cancer cell migration and invasion in prostate cancer.

Author information

1
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
2
Department of Urology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
3
Department of Urology, Teikyo University Chiba Medical Centre, Chiba 299-0111, Japan.
4
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan.

Abstract

BACKGROUND:

MicroRNA-224 (miR-224) and microRNA-452 (miR-452) are closely located on the human chromosome Xq28 region. miR-224 functions as a tumour suppressor by targeting tumour protein D52 (TPD52) in prostate cancer (PCa). Here, we aimed to investigate the functional significance of miR-452 in PCa cells.

METHODS:

Functional studies of PCa cells were performed using transfection with mature miRNAs or siRNAs. Genome-wide gene expression analysis, in silico analysis, and dual-luciferase reporter assays were applied to identify miRNA targets. The association between miR-452 levels and overall patient survival was estimated by the Kaplan-Meier method.

RESULTS:

Expression of miR-452 was significantly downregulated in PCa tissues. Transfection with mature miR-452 inhibited the migration and invasion of PCa cells. Kaplan-Meier survival curves showed that low expression of miR-452 predicted a short duration of progression to castration-resistant PCa. WW domain-containing E3 ubiquitin protein ligase-1 (WWP1) was a direct target of miR-452, and knockdown of WWP1 inhibited the migration and invasion of PCa cells. WWP1 was upregulated in PCa clinical specimens.

CONCLUSIONS:

Regulation of the miR-452-WWP1 axis contributed to PCa cell migration and invasion, and elucidation of downstream signalling of this axis will provide new insights into the mechanisms of PCa oncogenesis and metastasis.

PMID:
27070713
PMCID:
PMC4865980
DOI:
10.1038/bjc.2016.95
[Indexed for MEDLINE]
Free PMC Article

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