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miR-205 acts as a tumour radiosensitizer by targeting ZEB1 and Ubc13

Author

Listed:
  • Peijing Zhang

    (The University of Texas MD Anderson Cancer Center)

  • Li Wang

    (The University of Texas MD Anderson Cancer Center)

  • Cristian Rodriguez-Aguayo

    (The University of Texas MD Anderson Cancer Center)

  • Yuan Yuan

    (The University of Texas MD Anderson Cancer Center)

  • Bisrat G. Debeb

    (The University of Texas MD Anderson Cancer Center)

  • Dahu Chen

    (The University of Texas MD Anderson Cancer Center)

  • Yutong Sun

    (Department of Molecular and Cellular Oncology)

  • M. James You

    (The University of Texas MD Anderson Cancer Center)

  • Yongqing Liu

    (Molecular Targets Program, James Graham Brown Cancer Center, University of Louisville Health Sciences Center)

  • Douglas C. Dean

    (Molecular Targets Program, James Graham Brown Cancer Center, University of Louisville Health Sciences Center)

  • Wendy A. Woodward

    (The University of Texas MD Anderson Cancer Center)

  • Han Liang

    (The University of Texas MD Anderson Cancer Center)

  • Xianbin Yang

    (AM Biotechnologies)

  • Gabriel Lopez-Berestein

    (The University of Texas MD Anderson Cancer Center)

  • Anil K. Sood

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA)

  • Ye Hu

    (Houston Methodist Research Institute)

  • K. Kian Ang

    (The University of Texas MD Anderson Cancer Center)

  • Junjie Chen

    (The University of Texas MD Anderson Cancer Center
    Cancer Biology and Genes & Development Programs, Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston)

  • Li Ma

    (The University of Texas MD Anderson Cancer Center
    Cancer Biology and Genes & Development Programs, Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston)

Abstract

Tumour cells associated with therapy resistance (radioresistance and drug resistance) are likely to give rise to local recurrence and distant metastatic relapse. Recent studies revealed microRNA (miRNA)-mediated regulation of metastasis and epithelial–mesenchymal transition; however, whether specific miRNAs regulate tumour radioresistance and can be exploited as radiosensitizing agents remains unclear. Here we find that miR-205 promotes radiosensitivity and is downregulated in radioresistant subpopulations of breast cancer cells, and that loss of miR-205 is highly associated with poor distant relapse-free survival in breast cancer patients. Notably, therapeutic delivery of miR-205 mimics via nanoliposomes can sensitize the tumour to radiation in a xenograft model. Mechanistically, radiation suppresses miR-205 expression through ataxia telangiectasia mutated (ATM) and zinc finger E-box binding homeobox 1 (ZEB1). Moreover, miR-205 inhibits DNA damage repair by targeting ZEB1 and the ubiquitin-conjugating enzyme Ubc13. These findings identify miR-205 as a radiosensitizing miRNA and reveal a new therapeutic strategy for radioresistant tumours.

Suggested Citation

  • Peijing Zhang & Li Wang & Cristian Rodriguez-Aguayo & Yuan Yuan & Bisrat G. Debeb & Dahu Chen & Yutong Sun & M. James You & Yongqing Liu & Douglas C. Dean & Wendy A. Woodward & Han Liang & Xianbin Yan, 2014. "miR-205 acts as a tumour radiosensitizer by targeting ZEB1 and Ubc13," Nature Communications, Nature, vol. 5(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6671
    DOI: 10.1038/ncomms6671
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