Key Enzyme Discovered For Cancer Stem Cell Elimination: ADAR1

Key Enzyme Discovered For Cancer Stem Cell Elimination: ADAR1

As per a study published in Cancer Cell by researchers at the University of California San Diego School of Medicine, deregulation of stem cell enzyme ADAR1 provides therapeutic resistance in many malignancies. This Adenosine deaminase associated with RNA1 – ADAR1 enzyme can act as a therapeutic target for preventing cancer cell resistance to chemotherapy and radiations. ADAR1 has been seen active in more than 20 types of tumors known till date.

The ADAR enzyme act by modifying nucleotides in ds RNA molecules to regulate gene expression thus playing a fundamental role in the development of new stem cells.

Catriona Jamieson, MD, Ph.D., deputy director of the Sanford Stem Cell Clinical Center and deputy director of the UC San Diego Moores Cancer Center along with a team of scientists studied that malignant cells disrupt the normal functions of ADAR1 enzyme, initiating a series of molecular consequences that promote cancer stem cell regeneration at an increased rate.

In the Paper titled “Hyper-Editing of Cell-Cycle Regulatory and Tumor Suppressor RNA Promotes Malignant Progenitor Propagation” published in cancer cell the authors state that “Adenosine deaminase associated with RNA1 (ADAR1) deregulation contributes to therapeutic resistance in many malignancies. Here we

show that ADAR1-induced hyper-editing in normal human hematopoietic progenitors impairs miR-26a maturation, which represses CDKN1A expression indirectly via EZH2, thereby accelerating cell-cycle transit. However, in blast crisis chronic myeloid leukemia progenitors, loss of EZH2 expression and increased CDKN1A oppose cell-cycle transit,”.

“Moreover, A-to-I editing of both the MDM2 regulatory microRNA and its binding site within the 3′ UTR region stabilizes MDM2 transcripts, thereby enhancing blast crisis progenitor propagation. These data reveal a dual mechanism governing the malignant transformation of progenitors that is predicated on hyper-editing of cell-cycle-regulatory miRNAs and the 3′ UTR binding site of tumor suppressor miRNAs.”

A member of the team Qingfei Jiang, Ph.D., assistant project scientist in Jamieson’s lab said that they were successful in highlighting the functions of ADAR1 to ‘hyper-mutate’ tumor suppressor RNAs in leukemia and simultaneously edit the microRNA aimed at targeting the tumor suppressor RNA. Catriona Jamieson further added that the study involved tweaking the genetic blueprints and not rewriting them. Either way, the results will be dramatic.

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