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Autoregulatory suppression of c-Myc by miR-185-3p

Jun-Ming Liao1, Hua Lu

  • 1Department of Biochemistry and Molecular Biology and the Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

The Journal of Biological Chemistry
|August 12, 2011
PubMed

Insights

Researchers discovered microRNA-185-3p (miRNA) as a novel regulator of c-Myc. This miRNA feedback mechanism controls c-Myc levels, impacting cell proliferation in response to growth signals.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • c-Myc oncogene expression is transiently downregulated after growth stimulation.
  • The precise mechanisms controlling c-Myc downregulation are not fully understood.
  • MicroRNAs (miRNAs) are key regulators of gene expression.

Purpose of the Study:

  • To identify novel regulators of c-Myc expression.
  • To elucidate the role of miRNAs in c-Myc feedback regulation.
  • To investigate the impact of miR-185-3p on c-Myc-mediated proliferation.

Main Methods:

  • Identification of miRNA targets using RNA sequencing and bioinformatic analysis.
  • Validation of miRNA-target interactions via real-time PCR, luciferase reporter assays, and ChIP assays.
  • Functional studies involving miRNA overexpression and inhibition in human cancer cells.

Main Results:

  • miR-185-3p was identified as a direct target of c-Myc.
  • Overexpression of miR-185-3p reduced c-Myc protein levels and serum-induced c-Myc expression.
  • miR-185-3p targets the coding sequence of c-Myc mRNA, suppressing proliferation.
  • Inhibition of miR-185-3p reversed the downregulation of c-Myc expression.

Conclusions:

  • miR-185-3p acts as a novel feedback regulator of c-Myc.
  • This miRNA-mediated autoregulatory mechanism controls c-Myc levels in response to serum stimulation.
  • miR-185-3p plays a significant role in suppressing c-Myc-driven cell proliferation.

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