Evidence map›Paper›PMID 33531067›Full record

ArticleExperimental hematology & oncology2021

MicroRNA let-7b downregulates AML1-ETO oncogene expression in t(8;21) AML by targeting its 3'UTR.

Daniel T Johnson, Amanda G Davis, Jie-Hua Zhou, Edward D Ball, Dong-Er Zhang

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Experimental hematology & oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.0field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
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  7. Gene Transcription as a Therapeutic Target in Leukemia.International journal of molecular sciences · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Daniel T JohnsonMoores Cancer Center, University of California, La Jolla, San Diego, CA, USA.
Amanda G DavisMoores Cancer Center, University of California, La Jolla, San Diego, CA, USA.
Jie-Hua ZhouMoores Cancer Center, University of California, La Jolla, San Diego, CA, USA.
Edward D BallMoores Cancer Center, University of California, La Jolla, San Diego, CA, USA.
Dong-Er ZhangMoores Cancer Center, University of California, La Jolla, San Diego, CA, USA. dez@ucsd.edu.
Moores Cancer CenterUniversity of California, San Diego · US

Funding

GENETIC MECHANISMS AND REGULATIONT32GM007240 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAMPTON, RANDOLPH Y. · 1985 to 2019
$23.8M
Contemporary Approaches to Cancer Cell Signaling and CommunicationT32CA009523 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DONOGHUE, DANIEL J, YANG, JING · 1985 to 2025
$12.1M
Molecular Mechanism of Leukemogenesis Involving AML1-ETOR01CA104509 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ZHANG, DONG-ER · 2004 to 2025
$6.6M
AML1-ETO Regulation via the 3'UTR in t(8;21) Acute Myeloid LeukemiaF31CA228324 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JOHNSON, DANIEL THOMAS · 2018 to 2020
$116k
NCI NIH HHS F31 CA228324NCI NIH HHS F31CA228324NCI NIH HHS R01 CA104509NCI NIH HHS R01CA104509NCI NIH HHS T32 CA009523NCI NIH HHS T32CA009523NIGMS NIH HHS T32 GM007240
6 · The paper itself

Abstract

backgroundAcute myeloid leukemia (AML) with the t(8;21)(q22;q22) chromosomal translocation is among the most common subtypes of AML and produces the AML1-ETO (RUNX1-ETO, RUNX1-RUNX1T1) oncogenic fusion gene. AML1-ETO functions as an aberrant transcription factor which plays a key role in blocking normal hematopoiesis. Thus, the expression of AML1-ETO is critical to t(8;21) AML leukemogenesis and maintenance. Post-transcriptional regulation of gene expression is often mediated through interactions between trans-factors and cis-elements within transcript 3'-untranslated regions (UTR). AML1-ETO uses the 3'UTR of the ETO gene, which is not normally expressed in hematopoietic cells. Therefore, the mechanisms regulating AML1-ETO expression via the 3'UTR are attractive therapeutic targets.

methodsWe used RNA-sequencing of t(8;21) patients and cell lines to examine the 3'UTR isoforms used by AML1-ETO transcripts. Using luciferase assay approaches, we test the relative contribution of 3'UTR cis elements to AML1-ETO expression. We further use let-7b microRNA mimics and anti-let-7b sponges for functional studies of t(8;21) AML cell lines.

resultsIn this study, we examine the regulation of AML1-ETO via the 3'UTR. We demonstrate that AML1-ETO transcripts primarily use a 3.7 kb isoform of the ETO 3'UTR in both t(8;21) patients and cell lines. We identify a negative regulatory element within the AML1-ETO 3'UTR. We further demonstrate that the let-7b microRNA directly represses AML1-ETO through this site. Finally, we find that let-7b inhibits the proliferation of t(8;21) AML cell lines, rescues expression of AML1-ETO target genes, and promotes differentiation.

conclusionsAML1-ETO is post-transcriptionally regulated by let-7b, which contributes to the leukemic phenotype of t(8;21) AML and may be important for t(8;21) leukemogenesis and maintenance.

Indexed as

AML1-ETO (RUNX1-RUNX1T1)let-7miRNAt(8;21) acute myeloid leukemia

Identifiers

PMID33531067
PMCPMC7856722
OpenAlexW3128519011

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.