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Updated: Feb 11, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
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.
Abstract:
Expression levels of the miR-200 family of miRNAs are significantly reduced during the epithelial-to-mesenchymal transition (EMT) and consequent metastasis of ovarian and other cancers. Consistently, ectopic over-expression of miR-200 family miRNAs in mesenchymal-like cells reverses the process by converting treated cells to an epithelial phenotype, thereby reducing invasiveness and increasing sensitivity to chemotherapeutic drugs. To better understand the dynamics and molecular processes underlying miRNA-induced mesenchymal-to mesenchymal transition (MET), a time-course study was conducted where miRNA-induced morphological and molecular changes associated with MET were monitored over a period of 144 h. Morphological transition from an elongated mesenchymal-like to a cuboidal epithelial-like phenotype is maximized at 48 h with cells returning to the elongated phenotype by 144 h. Changes in the expression of >3000 genes, including many previously associated with epithelial-to-mesenchymal transition (EMT), are most pronounced at 48 h, and approach starting levels of expression by 144 h. The majority of these genes are not direct targets of miR-429. Targeted (siRNA) inhibition of key miR-429 regulated genes previously implicated as drivers of EMT/MET, do not recapitulate miR-429 induced MET indicating that the underlying molecular processes are complex.
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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