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Enzyme Could Be Key to Unlocking Cancer Resistance
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Researchers at the University of California San Diego School of Medicine have identified one specific molecule, ADAR1, which is active in more than 20 tumor types. The enzyme could provide a kind of molecular radar for early cancer detection and represent a new therapeutic target against disease resistance.

The ADAR (adenosine deaminase acting on RNA) genes encode a family of three enzymes. They manage gene expression by modifying nucleotides within double-stranded RNA molecules, acting as fundamental editors in the development of new stem cells. ADAR1, however, can be found in several forms of cancer, including liver, breast, and leukemia.

We were able to illuminate the abilities of ADAR1 to ‘hyper-mutate’ tumor suppressor RNAs in leukemia and, at the same time, edit the microRNA aimed at targeting the tumor suppressor RNA. This enzyme turns on cancer resistance via a domino effect on RNA instead of DNA”, noted first author Qingfei Jiang, PhD.

The team noticed that the normal functions of the ADAR1 enzyme are hijacked by pre-malignant cells, causing a series of molecular consequences which promote malignant transformation, dormant cancer stem cell generation and treatment resistance.

Catriona Jamieson, MD, Ph.D., deputy director of the Sanford Stem Cell Clinical Center and senior author described the RNA editing as “tweaking basic genetic blueprints”, as opposed to a complete rewrite.

One result of detection of malignant RNA editing could be exposing dormant cancer stem cells that often escape therapies that target dividing cells, which leads to therapeutic resistance and disease relapse, and also highlight ADAR as a potentially tractable target for cancer stem cell elimination”, added Dr. Jamieson.

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