Time-course analysis of microRNA-induced mesenchymal-to-epithelial transition underscores the complexity of the

Loukia N Lili1, Andrew D Huang1, Mengnan Zhang1

  • 1Integrated Cancer Research Center, School of Biological Sciences, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, GA 30309, USA.

Cancer Letters
|May 8, 2018
PubMed

Insights

The miR-200 family of microRNAs (miRNAs) reverses cancer cell metastasis. This study monitored miRNA-induced changes over 144 hours, revealing complex molecular processes underlying this transition.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • The miR-200 family of microRNAs (miRNAs) is downregulated during epithelial-to-mesenchymal transition (EMT) and cancer metastasis.
  • Overexpression of miR-200 family miRNAs can induce mesenchymal-to-epithelial transition (MET), reducing cancer cell invasiveness and enhancing chemosensitivity.

Purpose of the Study:

  • To investigate the temporal dynamics and molecular mechanisms of miRNA-induced MET.
  • To monitor morphological and gene expression changes over a 144-hour time course.

Main Methods:

  • Time-course study of miRNA-induced MET in cancer cells.
  • Monitoring of morphological changes from mesenchymal to epithelial phenotypes.
  • Analysis of gene expression changes for over 3000 genes.
  • siRNA inhibition of key EMT/MET-associated genes.

Main Results:

  • Morphological transition to an epithelial phenotype peaked at 48 hours, with a return to mesenchymal phenotype by 144 hours.
  • Significant gene expression changes (>3000 genes) were most pronounced at 48 hours and returned towards baseline by 144 hours.
  • Most affected genes were not direct targets of miR-429, and siRNA inhibition of these genes did not fully replicate miRNA-induced MET.

Conclusions:

  • MiRNA-induced MET involves complex molecular processes not solely dependent on direct target regulation.
  • The dynamic interplay of gene expression changes over time is crucial for the MET process.
  • Further research is needed to elucidate the intricate mechanisms driving miRNA-mediated MET in cancer.

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