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GATA3 and APOBEC3B are prognostic markers in adrenocortical carcinoma and APOBEC3B is directly transcriptionally regulated by GATA3

Authors
  • Gara, Sudheer Kumar
  • Tyagi, Monica Varun
  • Patel, Dhaval Thakkur
  • Gaskins, Kelli
  • Lack, Justin
  • Liu, Yi
  • Kebebew, Electron
Type
Published Article
Journal
Oncotarget
Publisher
"Impact Journals, LLC "
Publication Date
Sep 08, 2020
Volume
11
Issue
36
Pages
3354–3370
Identifiers
DOI: 10.18632/oncotarget.27703
PMID: 32934779
PMCID: PMC7486697
Source
PubMed Central
Keywords
License
Green

Abstract

Recent evidence has implicated APOBEC3B (Apolipoprotein B mRNA editing enzyme catalytic subunit 3B) as a source of mutations in breast, bladder, cervical, lung, head, and neck cancers. However, the role of APOBEC3B in adrenocortical carcinoma (ACC) and the mechanisms through which its expression is regulated in cancer are not fully understood. Here, we report that APOBEC3B is overexpressed in ACC and it regulates cell proliferation by inducing S phase arrest. We show high APOBEC3B expression is associated with a higher copy number gain/loss at chromosome 4 and 8 and TP53 mutation rate in ACC. GATA3 was identified as a positive regulator of APOBEC3B expression and directly binds the APOBEC3B promoter region. Both GATA3 and APOBEC3B expression levels were associated with patient survival. Our study provides novel insights into the function and regulation of APOBEC3B expression in addition to its known mutagenic ability.

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