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MicroRNAs, miR-154, miR-299-5p, miR-376a, miR-376c, miR-377, miR-381, miR-487b, miR-485-3p, miR-495 and miR-654-3p, mapped to the 14q32.31 locus, regulate proliferation, apoptosis, migration and invasion in metastatic prostate cancer cells

Oncogene volume 33, pages 5173–5182 (2014)Cite this article

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Abstract

miRNAs act as oncogenes or tumor suppressors in a wide variety of human cancers, including prostate cancer (PCa). We found a severe and consistent downregulation of miRNAs, miR-154, miR-299-5p, miR-376a, miR-376c, miR-377, miR-381, miR-487b, miR-485-3p, miR-495 and miR-654-3p, mapped to the 14q32.31 region in metastatic cell lines as compared with normal prostatic epithelial cells (PrEC). In specimens of human prostate (28 normals, 99 primary tumors and 13 metastases), lower miRNA levels correlated significantly with a higher incidence of metastatic events and higher prostate specific antigen (PSA) levels, with similar trends observed for lymph node invasion and the Gleason score. We transiently transfected 10 members of the 14q32.31 cluster in normal prostatic epithelial cell lines and characterized their affect on malignant cell behaviors, including proliferation, apoptosis, migration and invasion. Finally, we identified FZD4, a gene important for epithelial-to-mesenchymal transition in (PCa), as a target of miR-377.

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Abbreviations

miRNA:

MicroRNA

PCa:

Prostate cancer

PrEC:

normal prostatic epithelial cells

PSA:

prostate-specific antigen.

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Acknowledgements

This work has been mainly supported by AIRC grant (2013IG 13387) to EC and partially supported by AIRC (2011-IG11955) and Ministry of Education and Science of the Russian Federation (11.G34.31.0069) to GM. Research described in this article was also supported in part by Min. Salute (ric. Oncologica26/07), ‘IstitutoDermopaticodell'Immacolata’ (RF06 c.73, RF07 c.57, RF08 c.15, RF07 c.57) to GM.

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Authors and Affiliations

  1. Department Experimental Medicine and Surgery, University of Tor Vergata, Rome, Italy

    A Formosa, A M Lena, D Italiano, E Finazzi-Agro', S Bernardini, G Melino & E Candi

  2. IDI-IRCCS, Rome, Italy

    A Formosa & G Melino

  3. The Simons Center for Systems Biology, Institute for Advanced Study, Princeton, NJ, USA

    E K Markert & A J Levine

  4. Laboratory of Molecular Pharmacology, Saint-Petersburg Technological Institute, 26 Moskovsky Prospect, Petersburg, Russia

    A V Garabadgiu

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Formosa, A., Markert, E., Lena, A. et al. MicroRNAs, miR-154, miR-299-5p, miR-376a, miR-376c, miR-377, miR-381, miR-487b, miR-485-3p, miR-495 and miR-654-3p, mapped to the 14q32.31 locus, regulate proliferation, apoptosis, migration and invasion in metastatic prostate cancer cells. Oncogene 33, 5173–5182 (2014). https://doi.org/10.1038/onc.2013.451

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