Abstract:
: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 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.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Jiang Q,Isquith J,Zipeto MA,Diep RH,Pham J,Delos Santos N,Reynoso E,Chau J,Leu H,Lazzari E,Melese E,Ma W,Fang R,Minden M,Morris S,Ren B,Pineda G,Holm F,Jamieson Cdoi
10.1016/j.ccell.2018.11.017subject
Has Abstractpub_date
2019-01-14 00:00:00pages
81-94.e7issue
1eissn
1535-6108issn
1878-3686pii
S1535-6108(18)30538-5journal_volume
35pub_type
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