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RNA editing in late stage/aggressive cancers.

The role of edited AZIN1 in mediating tumor aggressiveness.

Antizyme Inhibitor 1 (AZIN1) is an essential regulator of cell cycle dynamics in both normal and tumor cells. AZIN1 promotes cancer growth by binding and neutralizing the tumor suppressor Antizyme. Recent attention has focused on the consequences of adenosine deaminase (ADAR1)-mediated AZIN1 mRNA editing.  ADAR1 amplification and upregulation is associated with increased tumor aggressiveness and poor patient outcomes.  An ADAR-catalyzed Adenosine to Inosine mRNA-editing event results in a single serine-to-glycine substitution at residue 367 of AZIN1 in multiple cancer types. AZIN1 editing is associated with the presence of AZIN1 in the nucleus and with increased aggressiveness/lower survival in hepatocellular carcinoma, gastric carcinoma, multiple myeloma and other tumors A pan-cancer analysis characterized A-to-I RNA editing of more than 6200 patients of 17 cancer types. They study suggested that a few A-to-I nonsynonymous RNA editing may be a ‘master’ driver event and play a critical functional role in different tumor contexts while they identified AZIN1 as the top editing site which has relevance for the most types of cancer (8 types). They also showed that RNA edited AZIN1 (edAZIN1) increases chemoresistance to several chemotherapeutic agents. For the first time, I have shown that in prostate cancer, the edAZIN1 induce cytoplasmic-to-nuclear translocation, and confer more aggressive behavior measured by higher metastasis, lower survival and higher Gleason score. I have mapped put the mechanism behind the edAZIN1-induced aggressiveness in prostate cancer.

Selected Publication:

  • Ghalali A, Wang L, Stopsack KH, Rice JM, Wu S, Wu CL, Zetter BR, Rogers MS. AZIN1 RNA editing alters protein interactions, leading to nuclear translocation and worse outcomes in prostate cancer. Exp Mol Med. 2022 Oct;54(10):1713-1726.