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Keywords:

  • c-Myc;
  • Dox;
  • E-cadherin;
  • EMT;
  • inducible;
  • miR-9

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.