A-to-I RNA Editing Up-regulates Human Dihydrofolate Reductase in Breast Cancer

Enzyme action behind drug-resistant breast cancer

25 September 2017

An enzyme that breaks down folic acid could be the key to resistance to chemotherapy for breast cancer.

Methotrexate is a chemotherapy agent which prevents folic acids from helping tumour cells to grow. However, tumours can develop resistance through increased levels of dihydrofolate reductase (DHFR), an enzyme which regulates folic acids. Researchers from Kanazawa University have found that an enzyme that converts adenosine to inosine in strands of RNA, called ADAR1, increases levels of DHFR in lab-grown breast cancer cells. Genetically modifying these cells to prevent ADAR1 activity reduced DHFR levels and increased the tumour’s reactivity to methotrexate.

The findings suggest that the gene controlling ADAR1 activity could be an additional target in breast cancer patients being treated with methotrexate.

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References

1. Journal of Biological Chemistry 292, 4873-4884 (2017). doi: 10.1074/jbc.m117.775684