c-Myc suppressed E-cadherin through miR-9 at the post-transcriptional level

Authors

  • Mei Liu,

    1. Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China
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  • Hongxia Zhu,

    1. Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China
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  • Shangbin Yang,

    1. Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China
    2. Department of Pathology, Ohio State University, 150 Hamilton Hall, 1645 Neil Ave, Columbus, Ohio 43210, USA
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  • Zaozao Wang,

    1. Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China
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  • Jinfeng Bai,

    1. Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China
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  • Ningzhi Xu

    Corresponding author
    • Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China
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Corresponding author: e-mail: xningzhi@public.bta.net.cn

Abstract

c-Myc oncoprotein is overexpressed in most human cancers and regulates different genes and pathways in different cell types. E-cadherin expression is repressed by MYC through a post-transcriptional mechanism, but the exact mechanism remains elusive. Since E-cadherin is a direct target of miR-9 and miR-9 can be activated by MYC and MYCN, this suggests that c-Myc negatively modulates E-cadherin through a microRNA pathway. We have established a c-Myc-inducible expression system in which the protein level and transcriptional activity of c-Myc is significantly upregulated upon doxycycline induction. Overexpressed c-Myc led to an EMT-like conversion in the T-REx-293 cells and resulted in a significant decrease in E-cadherin and an increase in Vimentin. Stem-loop RT-PCR showed elevated expression of miR-9 when c-Myc was induced to be overexpressed. Regarding the relationship of c-Myc, miR-9 and E-cadherin, the expression of miR-9 was curtailed by using antagomir-9 in induced overexpressing c-Myc. Restoration of E-cadherin expression became much stronger in the presence of c-Myc. Thus c-Myc represses E-cadherin at the post-transcriptional level through miR-9.

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