Could microRNAs prove to be cancer’s ultimate Achilles heel?

Its apparent pointlessness in the grand scheme of human biology earned it the label of ‘Junk DNA’.

However, in a study published today in Nature Medicine, researchers have provided the most compelling evidence yet that microRNA is anything but superfluous, and may in fact hold the key to cures for cancer as well as other diseases.

Researchers from Sydney’s Garvan Institute , Queensland Institute of Medical Research (QIMR) the San Francisco’s University of California (UCSF) have shown how the introduction of a microRNA inhibitor can be used to kill off cancer cells.

According to the Garvan Institute’s Dr Alex Swarbrick, who worked on the project, this is a genuine world first.

“People have used genetic tools to block RNAs in the past but no one knew whether we could make this step,” he told ALS. “This now puts micoRNAs firmly on the table a class of therapeutic targets.”

The study involved mice injected with cells bred with the neurological cancer neuroblastoma, which was chosen because some 99 percent of sufferers do not have an actual mutation of the P53 gene, which is the body’s chief tumour suppressor, or ‘guardian of the genome’. The researchers found that in the case of this cancer, a particular microRNA, microRNA 380, appears to disable this gene.

How it works is this.

When genes are transcribed, a copy of them is made in RNA. Looking at P53 in healthy cells, the P53 RNA holds the instructions to make P53 proteins, which then perform the role of tumour suppressant in cells. In the case of neuroblastoma, the researchers found that microRNA 380 binds with P53 RNA blocking its ability to make proteins. P53 proteins therefore reduce in number allowing the tumour to flourish.

Swarbrick said that the findings suggest the potential for cures to several common cancers which are known to rely on microRNA for their existence.

“We see high levels of microRNA in more common adult cancers, particularly brain cancers as well as some melanomas,” he said. “Cancer is highly addicted to this MicroRNA.”

The study was based on a pre-existing agent developed by San Diego-based microRNA specialist Regulus Therapeutics, meaning Swarvick said, that the path to regulatory approval would be much shorter than normal.

“Because the drug already exists we are one step ahead of where these studies usually are.”

“It might not take more than a couple of years.”

While many other methods for suppressing cancer tumours involve some form of genetic trickery, the study detailed today simply involved two weekly injections of the microRNA suppressor, indicating the potential for quite simple and effective treatments for human cancers in the future.

“Instead of poisoning the body with chemotherapy we hope to come up with specific drugs that attack cancer’s Achilles heel,” Swarbrick said.

Encouragingly, the researchers also found that while microRNA 380 plays an important role in early cell development, it is switched off healthy adult cells, meaning that suppressing it is therefore unlikely to cause worrying side effects.

Relatively rare in adults, neuroblastoma is one of the most common, and deadliest of all childhood cancers, and is the most common form of cancer in infants.

Swarbrick confirmed that he and his research team are in discussions with various health agencies around the world, including in the US, in the hope of gaining approval to administer the agent to children who are currently dangerously ill with the disease.