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A Lack of 'Editing' in The Brain Could Be What's Driving The Most Aggressive Tumours

This could explain a lot.

SIGNE DEAN
19 JUN 2017
 

Brain cancer is often a devastating diagnosis, and scientists have been hunting for mechanisms that could explain the sources of brain tumours, with hopes to also find something that could prevent them.

Now a new study has peered into the mechanisms of gene expression in the brain, and found that tissue samples from brain cancer patients show a lack of microRNA editing. This means we might one day find a way to use gene editing to slow down the progression of the disease.

 

MicroRNAs are short bits of RNA that don't code for proteins, but are still important for regulating gene expression. In fact, these molecules might be responsible for fine-tuning as much as 30 percent of all protein-encoding genes in mammals.

This fine-tuning happens through various changes to the RNA molecule, and this process is called 'editing'. Studies have shown that editing "changes the information encoded by the genome and adds complexity to the gene regulatory networks".

A common type of microRNA editing happens when one of its components, adenosine, is changed to a different one, inosine, lending the name 'A-to-I editing'.

Researchers know that A-to-I editing is a crucial process needed for normal functioning of the organism, especially when it comes to cell development and homeostasis.

Problems with microRNA editing, which lead to changes in gene expression, have already been linked to several types of cancer, including a type of brain cancer called glioma.

Now scientists have looked into the mechanisms behind microRNA editing in human brain tissue samples, looking specifically at the frontal cortex and corpus callosum, along with tumour samples of glioblastoma multiforme, a highly aggressive type of brain cancer.

 

The team found that brain tumour samples had significantly lower levels of A-to-I editing, while in healthy brains this process happens much more regularly, even in comparison to other types of tissue in the human body.

"What precisely is happening, we can't say, but with altered levels and positions of these editing events, cellular output can be significantly altered which we see in case of cancers," says lead researcher Arijit Mukhopadhyay from the CSIR-Institute of Genomics and Integrative Biology in India.

In other words, it looks like if microRNA editing goes off the rails and doesn't rearrange its components just so, it can lead to all kinds of genetic changes which in turn affect how the brain cells grow - sometimes for the worst.

Cancer happens when cells start dividing out of control and take over, so this new finding is an important step towards establishing what exactly goes wrong at the biochemical level when a brain tumour starts to form.

"[W]e have been able to show that in both healthy and diseased state, microRNA editing is an important layer of information with specific sequence and structural preferences – especially in the human brain," the team writes in the paper.

Scientists say they now need more research to further establish what happens in the brain to derail editing in a way that can lead to tumours. Conversely, they also hope to identify specific microRNA types that could protect us from cancer by suppressing tumour formation.

 

Armed with this knowledge, researchers could one day even use gene editing techniques like CRISPR to potentially fix the microRNA editing problems.

If this method can prevent the changes in cells that lead to cancer, it might be a way to prevent tumours from growing in the first place.

The study was published in Nature Scientific Reports.

 

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