08-Jan-2019 - University of California, San Diego

An errant editing enzyme promotes tumor suppressor loss and leukemia propagation

Researchers at University of California San Diego School of Medicine report that detection of "copy editing" by a stem cell enzyme called ADAR1, which is active in more than 20 tumor types, may provide a kind of molecular radar for early detection of malignancies and represent a new therapeutic target for preventing cancer cell resistance to chemotherapy and radiation.

Adenosine deaminases are a family of three enzymes encoded by the ADAR genes, which stand for adenosine deaminase acting on RNA. They regulate gene expression by modifying nucleotides within double stranded RNA molecules, serving as fundamental editors in the development of new stem cells.

The enzyme, however, is also activated in cancers as diverse as liver, breast and leukemia. A research team led by senior author Catriona Jamieson, MD, PhD, deputy director of the Sanford Stem Cell Clinical Center and deputy director of the UC San Diego Moores Cancer Center, found that the normal functions of the ADAR1 enzyme are hijacked by pre-malignant cells, leading to a cascade of molecular consequences that promote malignant transformation, dormant cancer stem cell generation and resistance to treatment.

"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," said first author Qingfei Jiang, PhD, assistant project scientist in Jamieson's lab.

Jamieson characterized RNA editing as tweaking basic genetic blueprints, not fundamentally rewriting them. Nonetheless, the results might be dramatic. "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," said Jamieson.

More about UCSD
  • News

    Cellular nanosponges could soak up SARS-CoV-2

    Scientists are working overtime to find an effective treatment for COVID-19, the illness caused by the new coronavirus, SARS-CoV-2. Many of these efforts target a specific part of the virus, such as the spike protein. Now, researchers reporting in Nano Letters have taken a different approac ... more

    Machine learning technique speeds up crystal structure determination

    Nanoengineers at the University of California San Diego have developed a computer-based method that could make it less labor-intensive to determine the crystal structures of various materials and molecules, including alloys, proteins and pharmaceuticals. The method uses a machine learning a ... more

    Autonomous Microtrap for Pathogens

    Antibiotics are more efficient when they can act on their target directly at the site of infestation, without dilution. In the journal Angewandte Chemie, American scientists describe a synthetic chemical trap that propels itself to its place of action in the body fluid and then lures the ba ... more

  • Videos

    Researchers use acoustic waves to move fluids at the nanoscale

    A team of mechanical engineers at the University of California San Diego has successfully used acoustic waves to move fluids through small channels at the nanoscale. The breakthrough is a first step toward the manufacturing of small, portable devices that could be used for drug discovery an ... more