A new study by two teams at MD Anderson Cancer Center discovered that a specific RNA editing technique contributes to protein variation in some cancers. The findings could lead to improved personalized therapies for cancer patients by identifying drugs that could inhibit problematic forms of a specific protein. The study was published in Cancer Cell.
Adenosine to inosine (A-to-I) editing is an RNA editing technique common in the human genome and occurs in double-stranded RNA regions where adenosine is modified to inosine by hydrolytic deamination. The altered RNA molecule results in a modified amino acid sequence in the translated protein. The mutant protein can misfold and cause functional problems within the cell. For example, the researchers identified a protein, COPA, had undergone A-to-I editing and the altered protein contributed to increased cancer cell proliferation, migration, and invasion in vitro. Overall, they demonstrated how small tweaks in amino acid sequence as a result of RNA editing leads to protein diversity in breast cancer.
"Using data from The Cancer Genome Atlas and the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium, our study provides large-scale direct evidence that A-to-I RNA editing is a source of proteomic diversity in cancer cells," said Liang. "RNA editing represents a new paradigm for understanding the molecular basis of cancer and developing strategies for precision cancer medicine. If a protein is only highly edited in tumor proteins, but not in normal proteins, then it's possible that a specific drug could be designed to inhibit the edited mutant protein."