研究故事

Cancer Genetic Laboratory’s discovery that ribonucleic acid editing can cause liver cancer gives new hope to patients.

A team from HKU’s Cancer Genetic Laboratory has discovered for the first time a ribonucleic acid (RNA) editing event which triggers the formation of liver cancer by transforming normal liver cells into tumour cells. Until now, there has been a great deal of focus on DNA mutations in tumour genesis and progression, but this breakthrough is the first to highlight the role of transcriptional changes in RNA in cancer.

Unlike some genetic mutations which are irreversible, RNA editing is potentially adjustable and therefore potentially rectifiable, offering the possibility of new hope to patients of liver cancer.

Researchers used the next-generation Transcriptome Sequencing Technique to search the RNAs. Samples from 200 local and Mainland liver cancer patients were examined by liver cells culture in-vitro and in experimental mouse models. Initially they discovered that a gene named AZIN1 was frequently excessively edited in tumour cells, but rarely in normal liver, blood and other organs. 

Further studies revealed that the RNA editing machinery, known as ADAR1, was deregulated in liver cells, which wrongly edited AZIN1 at high levels. This editing altered the protein coding sequence of AZIN1, making it capable of undergoing significant protein conformation and functional change. 

Clinicopathological data showed that RNA editing was significantly associated with the presence of liver cirrhosis, tumour recurrence, and reduced chances of survival for the patient, and that it transformed normal liver cells into tumour cells. 

Research leader and Professor of the Department of Clinical Oncology Professor Guan Xinyuan says: “RNA editing is a previously untouched field in cancer research. We are just at the very beginning and are putting together a puzzle that still has many missing pieces. The next step is to find other previously unidentified editing events in hepatocellular carcinoma (HCC) – now that we have discovered AZIN1, there may be other genes or micro-RNA or uncoding regions affected by RNA editing.”

“Moreover, we need to dig more deeply into the mechanisms of RNA editing. For example, what kind of molecules regulate this editing process, are there any co-factors, are there any etiologic factors affecting this process? Most importantly, we intend to test some small molecules which may target the RNA editing process to try to rectify the malfunction of that editing.”

"Ribonucleic acid editing is a previously untouched field in cancer research. We are just at the very beginning and are putting together a puzzle that still has many missing pieces."

Professor Guan Xinyuan

The full version of this article was originally published in Bulletin. Please click here to view this HKU publication.