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.
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.
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.
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.British Journal of Cancer advance online publication 12 April 2016; doi:10.1038/bjc.2016.95 www.bjcancer.com.
British journal of cancer. 2016 Apr 12 [Epub ahead of print]
Yusuke Goto, Satoko Kojima, Akira Kurozumi, Mayuko Kato, Atsushi Okato, Ryosuke Matsushita, Tomohiko Ichikawa, Naohiko Seki
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan., Department of Urology, Teikyo University Chiba Medical Centre, Chiba 299-0111, Japan., Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan., Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan., Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan., Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan., Department of Urology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan., Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.