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Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer

Oncogene volume 30, pages 4231–4242 (2011)Cite this article

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Abstract

The interaction between cancer cells and microenvironment has a critical role in tumor development and progression. Although microRNAs regulate all the major biological mechanisms, their influence on tumor microenvironment is largely unexplored. Here, we investigate the role of microRNAs in the tumor-supportive capacity of stromal cells. We demonstrated that miR-15 and miR-16 are downregulated in fibroblasts surrounding the prostate tumors of the majority of 23 patients analyzed. Such downregulation of miR-15 and miR-16 in cancer-associated fibroblasts (CAFs) promoted tumor growth and progression through the reduced post-transcriptional repression of Fgf-2 and its receptor Fgfr1, which act on both stromal and tumor cells to enhance cancer cell survival, proliferation and migration. Moreover, reconstitution of miR-15 and miR-16 impaired considerably the tumor-supportive capability of stromal cells in vitro and in vivo. Our data suggest a molecular circuitry in which miR-15 and miR-16 and their correlated targets cooperate to promote tumor expansion and invasiveness through the concurrent activity on stromal and cancer cells, thus providing further support to the development of therapies aimed at reconstituting miR-15 and miR-16 in advanced prostate cancer.

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Acknowledgements

We thank Giuseppe Loreto and Maria Rita Pulvirenti for technical assistance. This work was supported by the Italian Health Ministry with ‘Under forty researchers 2007’and Italy-USA programs and by the Italian Association for Cancer Research (AIRC).

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Author notes

  1. M Musumeci, V Coppola, R De Maria and D Bonci: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy

    M Musumeci, V Coppola, A Addario, M Patrizii, M Maugeri-Saccà, F Francescangeli, M Biffoni, M A Venneri, R De Maria & D Bonci

  2. Department of Experimental Oncology, Mediterranean Institute of Oncology, Catania, Italy

    L Memeo, C Colarossi & R De Maria

  3. Department of Urology, S. Giovanni Bosco Hospital, Turin, Italy

    D Collura, A Giacobbe, L D'Urso & G Muto

  4. AIDS National Center, Istituto Superiore di Sanità, Rome, Italy

    M Falchi

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Correspondence to R De Maria or D Bonci.

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Musumeci, M., Coppola, V., Addario, A. et al. Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer. Oncogene 30, 4231–4242 (2011). https://doi.org/10.1038/onc.2011.140

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