Oncotarget

Research Papers:

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

Sudheer Kumar Gara, Monica Varun Tyagi, Dhaval Thakkur Patel, Kelli Gaskins, Justin Lack, Yi Liu and Electron Kebebew _

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Oncotarget. 2020; 11:3354-3370. https://doi.org/10.18632/oncotarget.27703

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Abstract

Sudheer Kumar Gara1,*, Monica Varun Tyagi2,*, Dhaval Thakkur Patel3, Kelli Gaskins4, Justin Lack4, Yi Liu5 and Electron Kebebew2

1 Thoracic Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

2 The Department of Surgery and Stanford Cancer Institute, Stanford University, Stanford, CA, USA

3 Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA

4 Office of Science and Technology Resources, Frederick National Laboratory for Cancer Research, National Institutes of Health, Bethesda, MD, USA

5 Salubris Biotherapeutics, Gaithersburg, MD, USA

* These authors contributed equally to this work & first authors

Correspondence to:

Electron Kebebew,email: kebebew@stanford.edu

Keywords: adrenocortical carcinoma; APOBEC3B; GATA3; prognosis; DNA damage

Abbreviations: APOBEC3B: Apolipoprotein B mRNA editing enzyme catalytic subunit 3B; ACC: Adrenocortical carcinoma; ChIP: Chromatin immunoprecipitation

Received: May 09, 2020     Accepted: July 14, 2020     Published: September 08, 2020

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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