There’s been a deafening buzz lately surrounding a new focus of epigeneticists known as the epithelial-mesenchymal transition (EMT). EMT, the gateway between normal epithelial cells and those that gain mesenchymal properties, is thought to be the point where cancer metastasis kicks off. And now a University of Hong Kong team, led by Hongping Xia reports that miRNA-200a runs the show when it comes to keeping that dangerous transition in check.
While others have looked at the involvement of histone and DNA methylation in EMT, the Hong Kong group zeroed in on miR-200a’s role in cancer stem cell (CSC) creation in nasopharyngeal carcinoma (NPC). Through experiments with miR-200a over-expression and knockdown the researchers came away with several eye-opening kernels of information:
- Knockdown of miR-200a in NPC cells led to not just an EMT, but also a stem-like transition as well. The authors nicknamed it the epithelial-mesenchymal to stem-like transition, or EMST.
- miR-200a over-expression converts mesenchymal-like cells back to an epithelial state, and squashes stem-like features.
- EMST is controlled by miR-200a targeting of ZEB1 and CTNNB1 (ß-catenin)
- After knockdown by miR-200a, CTNNB1 re-expression brings back stem-like phenotypes that were lost.
The tenacious team’s research uncovered a new microRNA mechanism that reversibly shifts cell states and regulates the transition into metastasis.
Get all the details about how miR-200a keeps things in line at Journal of Biological Chemistry, November 2010.
Find out more about the miRZip™ miRNA inhibition constructs used in this paper at the System Bioscience website.