Singapore – Hong Kong - Scientists Discover How Editing Of RNA Leads To Cancer

A process that edits the genetic instructions for manufacturing proteins has been implicated in cancer for the first time.

A process that edits the genetic instructions for manufacturing proteins has been implicated in cancer for the first time.

The discovery, made by scientists in Hong Kong and Singapore, found that RNA editing of a specific protein may be responsible for turning normal liver cells into cancer cells.

The body’s genetic code is stored in DNA molecules that contain all the genes in the human genome. However, it is the protein product of each gene that is responsible for its carrying out its function in the cell.

To manufacture proteins, the genetic blueprint found in DNA molecules must be copied and sent to the cell’s protein-producing factories in the form of a message stored in RNA molecules. Proteins are then manufactured based on the genetic instructions found in the RNA message.

Scientists had previously identified a process, known as RNA editing, that changes the instructions found in the RNA message by substituting one alphabet of the code for another. This RNA editing process may cause the production of a protein that is structurally and functionally very different from the one that the genetic blueprint had intended.

Although other studies have suggested a link between RNA editing and cancer, it was not known if higher levels of RNA editing can promote cancer development.

In this study, published in Nature Medicine, the scientists used high-throughput sequencing technology to analyze the RNA messages found within liver tumors and compared them to those found in normal liver tissues.

Through their genomic analysis, the researchers identified a gene known as AZIN1 that showed high levels of RNA editing in the liver tumors compared to the normal tissues. Increased levels of edited AZIN1 RNA may be a cause of liver cancer as the RNA editing process changed the AZIN1 protein product into a form which promoted the development of cancer.

To verify their findings, the team analyzed samples from some 180 liver cancer patients in China and confirmed that around half of the tumors showed signs of increased AZIN1 RNA editing. They also found that RNA editing of the AZIN1 gene in tumours is significantly associated with the presence of liver cirrhosis, tumor recurrence, and poorer survival rate.

The discovery also raises the possibility of targeting abnormalities in the RNA message for cancer therapy.

“Up to now, scientists have focused on studying DNA, not RNA. Because RNA can be more easily modified than DNA, it suggests that therapeutic approaches are potentially available,” said Professor Daniel Tenen, a senior author of the study.

The article can be found at: Chen et al. (2013) Recoding RNA Editing Of AZIN1 Predisposes To Hepatocellular Carcinoma.

Source: NUS.

Tang Yew Chung | Health & Medicine

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