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Dysregulation of miRNAs-COUP-TFII-FOXM1-CENPF axis contributes to the metastasis of prostate cancer

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  • Shih-Chieh Lin

    (Baylor College of Medicine
    College of Medicine, National Cheng Kung University)

  • Chung-Yang Kao

    (Baylor College of Medicine)

  • Hui-Ju Lee

    (Baylor College of Medicine)

  • Chad J. Creighton

    (Baylor College of Medicine)

  • Michael M. Ittmann

    (Baylor College of Medicine)

  • Shaw-Jenq Tsai

    (College of Medicine, National Cheng Kung University
    Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University)

  • Sophia Y. Tsai

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Ming-Jer Tsai

    (Baylor College of Medicine
    Baylor College of Medicine)

Abstract

Although early detection and treatment of prostate cancer (PCa) improves outcomes, many patients still die of metastatic PCa. Here, we report that metastatic PCa exhibits reduced levels of the microRNAsmiR-101 and miR-27a. These micro-RNAs (miRNAs) negatively regulate cell invasion and inhibit the expression of FOXM1 and CENPF, two master regulators of metastasis in PCa. Interestingly, the repression of FOXM1 and CENPF by these miRNAs occurs through COUP-TFII, a member of the orphan nuclear receptors family. Loss of miR-101 positively correlates with the increase of COUP-TFII-FOXM1-CENPF activity in clinical PCa data sets, implicating clinical relevance of such regulation. Further studies show that COUP-TFII is a critical factor controlling metastatic gene networks to promote PCa metastasis. Most importantly, this miRNA-COUP-TFII-FOXM1-CENPF regulatory axis is also involved in the development of enzalutaminde resistance. Taken together, our findings highlight the contribution of specific miRNAs through the regulation of the COUP-TFII-FOXM1-CENPF cascade in PCa metastasis and drug resistance.

Suggested Citation

  • Shih-Chieh Lin & Chung-Yang Kao & Hui-Ju Lee & Chad J. Creighton & Michael M. Ittmann & Shaw-Jenq Tsai & Sophia Y. Tsai & Ming-Jer Tsai, 2016. "Dysregulation of miRNAs-COUP-TFII-FOXM1-CENPF axis contributes to the metastasis of prostate cancer," Nature Communications, Nature, vol. 7(1), pages 1-14, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11418
    DOI: 10.1038/ncomms11418
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