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MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes

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  • Can Liu

    (University of Texas MD Anderson Cancer Center
    Cancer Stem Cell Institute, Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine)

  • Ruifang Liu

    (University of Texas MD Anderson Cancer Center
    Cancer Stem Cell Institute, Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine
    Roswell Park Cancer Institute)

  • Dingxiao Zhang

    (University of Texas MD Anderson Cancer Center
    Roswell Park Cancer Institute)

  • Qu Deng

    (University of Texas MD Anderson Cancer Center
    Roswell Park Cancer Institute
    Program in Molecular Carcinogenesis, University of Texas Graduate School of Biomedical Sciences (GSBS))

  • Bigang Liu

    (University of Texas MD Anderson Cancer Center)

  • Hsueh-Ping Chao

    (University of Texas MD Anderson Cancer Center
    Program in Molecular Carcinogenesis, University of Texas Graduate School of Biomedical Sciences (GSBS))

  • Kiera Rycaj

    (University of Texas MD Anderson Cancer Center
    Roswell Park Cancer Institute)

  • Yoko Takata

    (University of Texas MD Anderson Cancer Center)

  • Kevin Lin

    (University of Texas MD Anderson Cancer Center)

  • Yue Lu

    (University of Texas MD Anderson Cancer Center)

  • Yi Zhong

    (University of Texas MD Anderson Cancer Center)

  • John Krolewski

    (Roswell Park Cancer Institute)

  • Jianjun Shen

    (University of Texas MD Anderson Cancer Center)

  • Dean G. Tang

    (University of Texas MD Anderson Cancer Center
    Cancer Stem Cell Institute, Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine
    Roswell Park Cancer Institute)

Abstract

MicroRNAs play important roles in regulating tumour development, progression and metastasis. Here we show that one of the miR-200 family members, miR-141, is under-expressed in several prostate cancer (PCa) stem/progenitor cell populations in both xenograft and primary patient tumours. Enforced expression of miR-141 in CD44+ and bulk PCa cells inhibits cancer stem cell properties including holoclone and sphere formation, as well as invasion, and suppresses tumour regeneration and metastasis. Moreover, miR-141 expression enforces a strong epithelial phenotype with a partial loss of mesenchymal phenotype. Whole-genome RNA sequencing uncovers novel miR-141-regulated molecular targets in PCa cells including the Rho GTPase family members (for example, CDC42, CDC42EP3, RAC1 and ARPC5) and stem cell molecules CD44 and EZH2, all of which are validated as direct and functionally relevant targets of miR-141. Our results suggest that miR-141 employs multiple mechanisms to obstruct tumour growth and metastasis.

Suggested Citation

  • Can Liu & Ruifang Liu & Dingxiao Zhang & Qu Deng & Bigang Liu & Hsueh-Ping Chao & Kiera Rycaj & Yoko Takata & Kevin Lin & Yue Lu & Yi Zhong & John Krolewski & Jianjun Shen & Dean G. Tang, 2017. "MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes," Nature Communications, Nature, vol. 8(1), pages 1-14, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14270
    DOI: 10.1038/ncomms14270
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