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Enzyme Identified as Contributor to Cancer Growth

Stem cells.

A stem cell enzyme, adenosine deaminase associated with RNA1 (ADAR1), has been identified as an active component of over 20 types of cancer, including liver, breast, and leukemia. A new test to detect ADAR1 could have the capability of being a potential way to screen for cancer.

Adenosine deaminase associated with RNA1 is one of three enzymes encoded by the ADAR genes. Because they modify nucleotides within double-stranded RNA molecules, in turn regulating gene expression, these enzymes are essential editors in the growth of new stem cells.

A research team headed by Catriona Jamieson, MD, PhD, Deputy Director of the Sanford Stem Cell Clinical Center and Deputy Director of the University of California San Diego Moores Cancer Center, revealed in a study published in Cancer Cell that malignant cancer cells take over the normal functions of the ADAR1 enzyme. This causes a myriad of problems: malignant growth, treatment resistance, and dormant cancer stem cell generation.

"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," reported the study's lead author, Qingfei Jiang, PhD, an Assistant Project Scientist in Dr. Jamieson's lab.

"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," explained Dr. Jamieson.

These results could potentially lead to cancer treatments that inhibit cancer cells from taking over the normal functions of the ADAR1 enzyme.

For More Information

Jiang Q, Isquith J, Zipeto MA, et al (2019). Hyper-editing of cell-cycle regulatory and tumor suppressor RNA promotes malignant progenitor propagation. Cancer Cell. [Epub ahead of print] DOI:10.1016/j.ccell.2018.11.017

Image courtesy of Nissim Benvenisty

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