Nitric oxide may contribute to cancer by turning off genes, study finds 

Nitric oxide is an important cell-signaling molecule in the body. It regulates blood pressure, immune response and the nervous system. But nitric oxide is not like other cellular signals. As a small free radical, it only exists for a few seconds but can move easily inside and across cells, controlling their function. 

A study from UIC researchers has found a substantial new way that nitric oxide can influence a cell and, more broadly, a person’s health. By switching genes off and on, the short-lived signal can have long-term effects on human health and disease, according to a team led by Douglas Thomas of UIC. That ability may explain nitric oxide’s known role in making certain types of cancers more deadly. 

The Nature Communications paper is the latest in a long line of research from Thomas’ laboratory on how nitric oxide can control epigenetics.  

“If your DNA is your hard drive, epigenetics is the software that controls your genetic program,” said Thomas, associate professor in the Retzky College of Pharmacy and member of the University of Illinois Cancer Center. By discovering nitric oxide’s effect on an epigenetic process called DNA methylation, “we’ve discovered basically an entirely new mechanism of nitric-oxide signaling.” 

In each cell, only a fraction of genes is turned on at any given time. One control switch used by cells is DNA methylation, where a small chemical group is added to or removed from genes to control their expression. 

In both normal and cancer cells, Thomas and colleagues found that nitric oxide acts as a molecular switch by increasing the methylation of DNA to turn specific genes on and off. Additional experiments found that nitric oxide causes this effect by blocking enzymes that normally remove methyl groups from genes. 

That disruption could produce serious health effects, particularly if the genes affected promote or suppress the progression of cancer. Indeed, cancers with tumors expressing high levels of nitric oxide synthase — the enzyme that makes nitric oxide in cells — have a high mortality rate. 

“If it’s turning on oncogenes or turning off tumor suppressors, then you can see how this effect might be making cancer worse,” Thomas said. 

In future research, Thomas’ group will look at how nitric oxide’s epigenetic effects change other cellular processes; nitric oxide is known to play a role in many other diseases. These affected pathways could inspire new therapeutics for cancer, cardiovascular disease and other conditions related to nitric oxide activity, he said. 

Additional UIC co-authors on the paper include Marianne Palczewski, Hannah Petraitis Kuschman, Aydolun Petenkaya and Constantinos Chronis. The work was funded by grants from the National Institutes of Health, the University of Illinois Chicago Department of Pharmaceutical Sciences Bridge Fund, Hans W. Vahlteich Bridge Fund, UICentre, and the University of Illinois Cancer Center.