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-beta-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.
[1]Chinese Acad Sci, Shanghai Adv Res Inst, Lab Syst Biol, Shanghai 200031, Peoples R China;
[2]Univ Chinese Acad Sci, Shanghai 200031, Peoples R China;
[3]Shanghai Univ, Sch Life Sci, Shanghai 200031, Peoples R China;
[4]Chinese Acad Sci, Biomed Big Data Ctr, CAS Key Lab Computat Biol,Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol,Shanghai Inst, Shanghai 200031, Peoples R China;
[5]Chinese Acad Sci, Key Lab Syst Biol, Ctr Excellence Mol Cell Sci, Inst Biochem & Cell Biol,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China;
[6]Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China;
[7]ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China;
[8]Fudan Univ, Shanghai Canc Ctr, Dept Breast Surg, Key Lab Breast Canc Shanghai, Shanghai 200032, Peoples R China;
[9]Fudan Univ, Precis Canc Med Ctr, Shanghai Canc Ctr, Shanghai 200032, Peoples R China;
[10]Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Kunming 650223, Yunnan, Peoples R China;
[11]Res Ctr Brain Sci & Brain Inspired Intelligence, Shanghai 201210, Peoples R China
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