A microRNA with context-dependent effects

The worldwide pandemic of obesity leads to severe metabolic liver disorders. When fat starts to accumulate in the liver, it can lead to liver inflammation and fibrosis with cancer as an end stage. After decades of research on genetic mutations, scientists are now looking for other alterations that could explain the apparition and progression of these disorders. Some tiny non-coding nucleic acids called microRNAs open promising therapeutic avenues as they regulate the expression of hundreds of genes at once. However, neither the exact network of proteins targeted by each microRNA, nor their regulation mechanisms are fully understood.


The story of microRNA-22

One of these microRNAs, microRNA-22, is of particular interest as it is highly expressed in the liver. In their recent study published in the Journal of Personalized Medicine, scientists from Prof. Michelangelo Foti laboratory discovered that microRNA-22 governs key aspects of liver metabolism. Its fine-tuning regulation of a whole network of genes involved in fat and sugar metabolism might explain its role in metabolic liver disorders.


The fine-tuning regulation of a whole network of genes involved in fat (lipid) and sugar (glucose) metabolism by microRNA-22 might explain its role in metabolic liver. © Gjorgjieva et al. 2020, Journal of Personalized Medicine.


When the context matters

Investigating more deeply the role of microRNA-22 in earlier stages of metabolic diseases, scientists from the laboratory of Prof. Michelangelo Foti discovered that microRNA-22 does not function in the same way in all organs. Researchers discovered also that the role of microRNA-22 changed also according to the food or energy intake. Indeed, the absence of microRNA-22 had no negative impact under normal diet, but leads to an exacerbated accumulation of fat in the liver with a food intake rich in fat.


What’s next?

This context- and organ-dependence reinforces the importance not to conclude to the therapeutic effect of a molecule on the basis of a single study in one particular organ. Researchers are now turning their efforts to understand how microRNA-22 alterations impact the progression of metabolic liver diseases towards liver cancer. In this way, they hope to find new therapeutic issues to fight the development of liver cancer.



9 Nov 2020