Adenosine deaminases are a family of three enzymes encoded by the ADAR genes, and researchers have found that editing enzyme promotes tumour suppressor loss and leukaemia propagation.
Researchers at University of California San Diego School of Medicine, USA, report that detection of ‘copy editing’ by a stem cell enzyme called ADAR1, derived from adenosine deaminases, which is active in more than 20 different tumour 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.
What do you know about adenosine deaminases?
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 leukaemia. Researchers found that the normal functions of the ADAR1 enzyme are hijacked by pre-malignant cells, leading to a torrent of molecular consequences that promote malicious transformation, dormant cancer stem cell generation and resistance to treatment.
Qingfei Jiang, PhD, assistant project scientist explains: “We were able to illuminate the abilities of ADAR1 to ‘hyper-mutate’ tumour suppressor RNAs in leukemia and, at the same time, edit the microRNA aimed at targeting the tumour suppressor RNA. This enzyme turns on cancer resistance via a domino effect on RNA instead of DNA.”
Catriona Jamieson, MD, PhD, deputy director of the Sanford Stem Cell Clinical Center and deputy director of the UC San Diego Moores Cancer Centre characterised RNA editing as tweaking basic genetic blueprints, not fundamentally rewriting them. Nevertheless, the results might be dramatic.
She adds: “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.”