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Glucocorticoids mediate induction of microRNA-708 to suppress ovarian cancer metastasis through targeting Rap1B

Author

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  • Kai-Ti Lin

    (Institute of Molecular and Genomic Medicine, National Health Research Institutes)

  • Yu-Ming Yeh

    (Institute of Molecular and Genomic Medicine, National Health Research Institutes)

  • Chi-Mu Chuang

    (Taipei Veterans General Hospital
    Institute of Clinical Medicine, School of Medicine, National Yang-Ming University)

  • Scarlett Y. Yang

    (Institute of Molecular and Genomic Medicine, National Health Research Institutes)

  • Jer-Wei Chang

    (Institute of Molecular and Genomic Medicine, National Health Research Institutes)

  • Shu-Pin Sun

    (Institute of Molecular and Genomic Medicine, National Health Research Institutes)

  • Yi-Shiang Wang

    (Institute of Molecular and Genomic Medicine, National Health Research Institutes
    Institute of Molecular Medicine, National Tsing-Hua University)

  • Kuan-Chong Chao

    (Taipei Veterans General Hospital)

  • Lu-Hai Wang

    (Institute of Molecular and Genomic Medicine, National Health Research Institutes)

Abstract

Glucocorticoids are widely used in conjunction with chemotherapy for ovarian cancer to prevent hypersensitivity reactions. Here we reveal a novel role for glucocorticoids in the inhibition of ovarian cancer metastasis. Glucocorticoid treatments induce the expression of miR-708, leading to the suppression of Rap1B, which result in the reduction of integrin-mediated focal adhesion formation, inhibition of ovarian cancer cell migration/invasion and impaired abdominal metastasis in an orthotopic xenograft mouse model. Restoring Rap1B expression reverts glucocorticoid-miR-708 cascade-mediated suppression of ovarian cancer cell invasion and metastasis. Clinically, low miR-708 and high Rap1B are found in late-state ovarian tumours, as compared with normal, and patients with high miR-708 show significantly better survival. Overall, our findings reveal an opportunity for glucocorticoids and their downstream mediators, miR-708 or Rap1B, as therapeutic modalities against metastatic ovarian epithelial cancer.

Suggested Citation

  • Kai-Ti Lin & Yu-Ming Yeh & Chi-Mu Chuang & Scarlett Y. Yang & Jer-Wei Chang & Shu-Pin Sun & Yi-Shiang Wang & Kuan-Chong Chao & Lu-Hai Wang, 2015. "Glucocorticoids mediate induction of microRNA-708 to suppress ovarian cancer metastasis through targeting Rap1B," Nature Communications, Nature, vol. 6(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms6917
    DOI: 10.1038/ncomms6917
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