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Updated: May 14, 2026

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Published on: October 27, 2020
c-Myc suppressed E-cadherin through miR-9 at the post-transcriptional level
Mei Liu1, Hongxia Zhu, Shangbin Yang
1Laboratory 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, PR China.
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.
Insights
The c-Myc oncoprotein represses E-cadherin expression post-transcriptionally via microRNA-9 (miR-9). This study elucidates a novel mechanism linking c-Myc, miR-9, and E-cadherin regulation in cancer.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- c-Myc oncoprotein is frequently overexpressed in human cancers.
- The mechanism by which c-Myc represses E-cadherin post-transcriptionally is not fully understood.
- E-cadherin is a known target of miR-9, and miR-9 can be activated by MYC/MYCN.
Purpose of the Study:
- To investigate the role of the microRNA pathway in c-Myc-mediated repression of E-cadherin.
- To elucidate the precise mechanism of c-Myc's negative modulation of E-cadherin expression.
Main Methods:
- Established a doxycycline-inducible c-Myc expression system in T-REx-293 cells.
- Utilized stem-loop RT-PCR to assess miR-9 expression levels.
- Employed antagomir-9 to inhibit miR-9 activity in cells overexpressing c-Myc.
Main Results:
- Overexpression of c-Myc induced an epithelial-to-mesenchymal transition (EMT)-like phenotype, decreasing E-cadherin and increasing Vimentin.
- Induced c-Myc overexpression led to significantly elevated miR-9 levels.
- Inhibition of miR-9 using antagomir-9 partially restored E-cadherin expression in the presence of c-Myc.
Conclusions:
- c-Myc represses E-cadherin expression at the post-transcriptional level.
- The microRNA-9 pathway is a key mediator of c-Myc's effect on E-cadherin.
- This finding provides a novel insight into cancer progression and potential therapeutic targets.
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