Genome-wide expression changes mediated by A-to-I RNA editing correlate with hepatic oncogenesis

Adenosine-to-inosine (A-to-I) RNA editing is one of the most prevalent RNA modifications in the animal kingdom. Since inosine is recognized as guanosines, the A-to-I process mimics A-to-G DNA mutations but can be controlled in a more flexible manner compared to DNA alterations.

We parsed the transcriptomes and translatomes of liver cancer and normal tissues from ten patients. We profiled the landscape of the A-to-I RNA editome in these samples and interrogated whether the A-to-I processes participated in the gene expression regulation in oncogenesis.

Globally, editing activity was enhanced in all tumor samples compared to that in normal samples. Accordingly, expression of the gene encoding the RNA editing enzyme ADAR (adenosine deaminase acting on RNA) was elevated. Two intronic self-editing sites in ADAR mRNAs controlled its splicing pattern and may regulate its translation efficiency (TE). Moreover, the expression of oncogenes was generally upregulated in tumors, whereas tumor suppressor genes (TSG) were downregulated, possibly due to alterations to microRNA binding sites or RNA splicing defects caused by A-to-I editing.

A-to-I RNA editing plays a crucial role in the oncogenesis of liver cancer. ADAR regulates its own expression via self-editing, and it also affects global transcriptomes and translatomes involving cancer-related genes by RNA editing and changing their expression patterns.