During an embryo's development, epithelial cells can break away from the cell cluster, modify their cell type-specific properties, and migrate into other regions to form the desired structures there. This process, which is known as an epithelial-mesenchymal transition (EMT), is reversible and can also proceed in the direction from mesenchymal cells to epithelial cells (MET). It is repeated multiple times during embryonic development and ultimately paves the way for the formation of organs in the human body.

Although this is a completely normal process during embryogenesis, it also plays an important role in the spread of tumor cells within the body and in the formation of metastases. As a result, this cellular program has also attracted greater attention in the field of tumor research in recent years.

Tumor cells are able to reactivate the EMT/MET program. By doing so, they obtain characteristics of stem cells and develop increased resistance to not only classical but also state-of-the-art targeted cancer therapies.

An EMT also makes it easier for cancer cells to break away from the primary tumor, to penetrate into surrounding tissue and into blood vessels, to spread throughout the body and to form metastases in distant organs, which is ultimately responsible for the death of most cancer patients.

In a study published in Nature Communications, the researchers focused specifically on microRNAs (miRNAs), a class of very short non-coding RNAs with a considerable effect on gene regulation. They identified a hitherto unknown microRNA, miR-1199-5p, that induces epithelial cell behavior and impedes the malignancy of tumor cells, as well as their potential to form secondary tumors.

Authors report that miR-1199-5p is downregulated in its expression during an epithelial–mesenchymal transition, while its forced expression prevents an epithelial–mesenchymal transition, tumor cell migration and invasion in vitro, and lung metastasis in vivo.

In concrete terms, the newly discovered microRNA prevents the synthesis of a specific protein, the transcription factor Zeb1, which activates EMT/MET - but if it is missing, the EMT process is prevented. Zeb1 also suppresses the expression of miR1199-5p in what is known as a negative feedback loop, whereby the two molecules regulate one another reciprocally.

https://www.unibas.ch/en/News-Events/News/Uni-Research/Newly-Discovered-microRNA-Regulates-Mobility-of-Tumor-Cells.html

https://www.nature.com/articles/s41467-017-01197-w