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KMID : 0620920220540101713
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Experimental & Molecular Medicine
2022 Volume.54 No. 10 p.1713 ~ p.1726
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AZIN1 RNA editing alters protein interactions, leading to nuclear translocation and worse outcomes in prostate cancer
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Ghalali Aram
Wang Liangzhe
Stopsack Konrad H.
Rice James M.
Wu Shulin
Wu Chin-Lee
Zetter Bruce R.
Rogers Michael S.
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Abstract
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The transcript encoding Antizyme Inhibitor 1 (AZIN1) is frequently edited in various cancers, and this editing is associated with enhanced tumor aggressiveness. After comparison of wild-type AZIN1 (wtAZIN1) and edited AZIN1 (edAZIN1, which contains a Ser367Gly substitution), we report differential binding of edAZIN1 to a small set of proteins; specifically, edAZIN1 binds to alpha-smooth muscle actin (ACTA2), gamma actin 1 (ACTG1), and myosin9, whereas wtAZIN1 does not. This binding enables nuclear translocation of edAZIN1. In contrast to overexpression of edAZIN1 and, to a lesser extent, (editable) wtAZIN1, overexpression of an uneditable AZIN1 allele does not promote a cellular phenotype associated with increased tumorigenicity. In patients, both editing and nuclear localization of AZIN1 are common and are associated with tumor aggressiveness, i.e., a higher Gleason score, higher genomic instability, and a shorter progression-free survival time. In conclusion, the data indicate that binding of edAZIN1 to the actin/myosin9 complex supports its nuclear translocation, leading to enhanced cellular aggressiveness, and is associated with worse prostate cancer outcomes.
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KEYWORD
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Oncogenesis, Prostate cancer
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