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

Yuwei Liu, Mengzhu Xue, Shaowei Du, Wanwan Feng, Ke Zhang, Liwen Zhang, Haiyue Liu, Guoyi Jia, Lingshuang Wu, Xin Hu (), Luonan Chen () and Peng Wang ()
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Yuwei Liu: Chinese Academy of Sciences
Mengzhu Xue: Chinese Academy of Sciences
Shaowei Du: Chinese Academy of Sciences
Wanwan Feng: Chinese Academy of Sciences
Ke Zhang: Chinese Academy of Sciences
Liwen Zhang: University of Chinese Academy of Sciences
Haiyue Liu: Chinese Academy of Sciences
Guoyi Jia: Chinese Academy of Sciences
Lingshuang Wu: ShanghaiTech University
Xin Hu: Fudan University
Luonan Chen: Chinese Academy of Sciences
Peng Wang: Chinese Academy of Sciences

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-09649-1

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