, a Novel RUNX1 Target Gene, is Down-regulated by RUNX1-ETO

Overview

Journal BBA Adv

Specialty Biochemistry

Date 2023 Apr 21

PMID 37082605

Authors

Akifumi Matsumoto

Tatsushi Yoshida

Takahiro Shima

Kenta Yamasaki

Kenjiro Tadagaki

Noriko Kondo

Yasumichi Kuwahara

Dong-Er Zhang

Tsukasa Okuda

Affiliations

Soon will be listed here.

Abstract

The fusion protein RUNX1-ETO is an oncogenic transcription factor generated by t(8;21) chromosome translocation, which is found in FAB-M2-type acute myeloid leukemia (AML). RUNX1-ETO is known to dysregulate the normal RUNX1 transcriptional network, which should involve essential factors for the onset of AML with t(8;21). In this study, we screened for possible transcriptional targets of RUNX1 by reanalysis of public data , and identified as a novel RUNX1 target gene because its expression was down-regulated in the presence of RUNX1-ETO. The expression level of was low in AML patient samples with t(8;21) and in Kasumi-1 cells, which carry RUNX1-ETO. Knockdown of RUNX1-ETO in Kasumi-1 cells restored expression, whereas overexpression of RUNX1 up-regulated expression. In addition, knockdown of RUNX1 in other human leukemia cells without RUNX-ETO, such as K562, led to a decrease in expression. Of note, the promoter sequence contains a consensus sequence for RUNX1 binding and it was activated by exogenously expressed RUNX1 based on our luciferase reporter assay. This luciferase signal was dominantly suppressed by RUNX1-ETO and site-directed mutagenesis of the consensus site abrogated the reporter activity. This study demonstrated that is a novel transcriptional target of RUNX1 and RUNX1-ETO suppressed transcription in t(8;21) AML. Thus, through this approach, we identified a novel transcriptional target of RUNX1, and the depletion of , the target gene, may be associated with the onset of t(8;21) AML.

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