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.

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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