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Competitive endogenous RNA is an intrinsic component of EMT regulatory circuits and modulates EMT

Author

Listed:
  • Yuwei Liu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Mengzhu Xue

    (Chinese Academy of Sciences)

  • Shaowei Du

    (Chinese Academy of Sciences
    Shanghai University)

  • Wanwan Feng

    (Chinese Academy of Sciences)

  • Ke Zhang

    (Chinese Academy of Sciences)

  • Liwen Zhang

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Haiyue Liu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Guoyi Jia

    (Chinese Academy of Sciences
    Shanghai University)

  • Lingshuang Wu

    (ShanghaiTech University)

  • Xin Hu

    (Fudan University
    Fudan University Shanghai Cancer Center)

  • Luonan Chen

    (Chinese Academy of Sciences
    ShanghaiTech University
    Chinese Academy of Sciences
    Research Center for Brain Science and Brain-Inspired Intelligence)

  • Peng Wang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences
    Fudan University)

Abstract

The competitive endogenous RNA (ceRNA) hypothesis suggests an intrinsic mechanism to regulate biological processes. However, whether the dynamic changes of ceRNAs can modulate miRNA activities remains controversial. Here, we examine the dynamics of ceRNAs during TGF-β-induced epithelial-to-mesenchymal transition (EMT). We observe that TGFBI, a transcript highly induced during EMT in A549 cells, acts as the ceRNA for miR-21 to modulate EMT. We further identify FN1 as the ceRNA for miR-200c in the canonical SNAIL-ZEB-miR200 circuit in MCF10A cells. Experimental assays and computational simulations demonstrate that the dynamically induced ceRNAs are directly coupled with the canonical double negative feedback loops and are critical to the induction of EMT. These results help to establish the relevance of ceRNA in cancer EMT and suggest that ceRNA is an intrinsic component of the EMT regulatory circuit and may represent a potential target to disrupt EMT during tumorigenesis.

Suggested Citation

  • Yuwei Liu & Mengzhu Xue & Shaowei Du & Wanwan Feng & Ke Zhang & Liwen Zhang & Haiyue Liu & Guoyi Jia & Lingshuang Wu & Xin Hu & Luonan Chen & Peng Wang, 2019. "Competitive endogenous RNA is an intrinsic component of EMT regulatory circuits and modulates EMT," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09649-1
    DOI: 10.1038/s41467-019-09649-1
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