An international team of scientists has studied the physiological functions of exosomal microRNAs (miRNAs). Their work will come in handy in the treatment of non-small cell lung cancer (NSCLC). This is reported by Free News with reference to an article about the study in the Journal of Extracellular Vesicles.
Most cases of non-small cell lung cancer are associated with overexpression of the pro-inflammatory lipid mediator prostaglandin E₂ (PGE₂), which promotes tumor growth. In a new study, scientists have shown that PGE₂ increases exosomal secretion of miR-574-5p miRNAs in lung cancer cells.
All cells in a multicellular organism must precisely coordinate their actions for the body to function properly. This applies to both healthy tissues and tumors. Communication between cells is carried out through direct cell contact or using messenger substances. Recent studies have shown that cells release extracellular vesicles – exosomes ranging in size from 50 to 200 nanometers – into the environment, which play a key role in cell-to-cell communication.
For a long time, these vesicles had little biological significance. It was assumed that the cells used them to dispose of unnecessary molecules. However, it is now known that these “bubbles” are important for the regulation of various physiological processes and diseases, such as cancer.
In cell communication, microRNA in exosomes plays a particularly important role. MicroRNAs are small molecules of ribonucleic acid that play a key role in regulating gene expression and cellular protein synthesis.
The research team, led by Dr. Meike Saul of the Department of Biology at the TU Darmstadt, is studying the physiological functions of these exosomal microRNAs and has recently made great strides in their research on lung cancer. This type of cancer is one of the most common in the world. Non-small cell lung cancer is the most common type of lung cancer and accounts for about 80% of all cases.
It is known that most cases of NSCLC are associated with overexpression of the proinflammatory lipid mediator prostaglandin E₂ (PGE₂), which actively promotes tumor growth. The extent to which tumor and inflammation-stimulating lipid mediators affect communication between cells via exosomes has not yet been investigated. In a new study, an international team of scientists has demonstrated for the first time that PGE₂ increases exosomal secretion of miR-574-5p miRNAs in lung cancer cells.
In addition, scientists have found that miR-574-5p, transported in exosomes, activates an immune receptor that lowers PGE₂ levels. This function in exosomes differs from that of the intracellular miR-574-5p, which initiates PGE₂ biosynthesis. The study showed that a combination of intracellular and exosomal miR-574-5p controls PGE₂ levels through a feedback loop. This means that the new discovery can be used to influence tumor growth.
There are various subtypes of non-small cell lung cancer. It turned out that in one of the most common types, adenocarcinoma, exosomal miR-574-5p affects PGE₂ biosynthesis. The researchers speculate that this is due to the unique composition of various proteins on the surface of exosomes.
In the new work, scientists have shown for the first time that the function of microRNA inside the cell can be radically different from its function in the exosome. Depending on the uptake mechanism, exosomal microRNA can be released at different locations within the cell. This decisively affects the function of the ribonucleic acid molecules.
Recently discovered link between miR-574-5p and PGE₂. opens up new therapeutic options for the treatment of lung cancer. “The results will form the basis for the development of innovative and personalized therapies,” explains Meike Saulo from the Department of Biology at the TU Darmstadt, who led the study. “Combining standard cancer therapies with inhibitors of PGE₂ synthesis is a very promising treatment strategy.”