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Runt-Related Transcription Factor 3 Promotes Acute Myeloid Leukemia Progression

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with high relapse/refractory rate. Genetic and epigenetic abnormalities are driving factors for leukemogenesis. RUNX1 and RUNX2 from the Runt-related transcription factor (RUNX) family played important roles in AML pathogenesis....

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Autores principales: Zhang, Wenwen, Ma, Qian, Long, Bing, Sun, Zhangyi, Liu, Lingling, Lin, Dongjun, Zhao, Minyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8549545/
https://www.ncbi.nlm.nih.gov/pubmed/34722267
http://dx.doi.org/10.3389/fonc.2021.725336
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author Zhang, Wenwen
Ma, Qian
Long, Bing
Sun, Zhangyi
Liu, Lingling
Lin, Dongjun
Zhao, Minyi
author_facet Zhang, Wenwen
Ma, Qian
Long, Bing
Sun, Zhangyi
Liu, Lingling
Lin, Dongjun
Zhao, Minyi
author_sort Zhang, Wenwen
collection PubMed
description Acute myeloid leukemia (AML) is an aggressive hematological malignancy with high relapse/refractory rate. Genetic and epigenetic abnormalities are driving factors for leukemogenesis. RUNX1 and RUNX2 from the Runt-related transcription factor (RUNX) family played important roles in AML pathogenesis. However, the relationship between RUNX3 and AML remains unclear. Here, we found that RUNX3 was a super-enhancer-associated gene and highly expressed in AML cells. The Cancer Genome Atlas (TCGA) database showed high expression of RUNX3 correlated with poor prognosis of AML patients. We observed that Runx3 knockdown significantly inhibited leukemia progression by inducing DNA damage to enhance apoptosis in murine AML cells. By chromatin immunoprecipitation sequencing (ChIP-seq) analysis, we discovered that RUNX3 in AML cells mainly bound more genes involved in DNA-damage repair and antiapoptosis pathways compared to that in normal bone marrow cells. Runx3 knockdown obviously inhibited the expression of these genes in AML cells. Overall, we identified RUNX3 as an oncogene overexpressed in AML cells, and Runx3 knockdown suppressed AML progression by inducing DNA damage and apoptosis.
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spelling pubmed-85495452021-10-28 Runt-Related Transcription Factor 3 Promotes Acute Myeloid Leukemia Progression Zhang, Wenwen Ma, Qian Long, Bing Sun, Zhangyi Liu, Lingling Lin, Dongjun Zhao, Minyi Front Oncol Oncology Acute myeloid leukemia (AML) is an aggressive hematological malignancy with high relapse/refractory rate. Genetic and epigenetic abnormalities are driving factors for leukemogenesis. RUNX1 and RUNX2 from the Runt-related transcription factor (RUNX) family played important roles in AML pathogenesis. However, the relationship between RUNX3 and AML remains unclear. Here, we found that RUNX3 was a super-enhancer-associated gene and highly expressed in AML cells. The Cancer Genome Atlas (TCGA) database showed high expression of RUNX3 correlated with poor prognosis of AML patients. We observed that Runx3 knockdown significantly inhibited leukemia progression by inducing DNA damage to enhance apoptosis in murine AML cells. By chromatin immunoprecipitation sequencing (ChIP-seq) analysis, we discovered that RUNX3 in AML cells mainly bound more genes involved in DNA-damage repair and antiapoptosis pathways compared to that in normal bone marrow cells. Runx3 knockdown obviously inhibited the expression of these genes in AML cells. Overall, we identified RUNX3 as an oncogene overexpressed in AML cells, and Runx3 knockdown suppressed AML progression by inducing DNA damage and apoptosis. Frontiers Media S.A. 2021-10-12 /pmc/articles/PMC8549545/ /pubmed/34722267 http://dx.doi.org/10.3389/fonc.2021.725336 Text en Copyright © 2021 Zhang, Ma, Long, Sun, Liu, Lin and Zhao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Zhang, Wenwen
Ma, Qian
Long, Bing
Sun, Zhangyi
Liu, Lingling
Lin, Dongjun
Zhao, Minyi
Runt-Related Transcription Factor 3 Promotes Acute Myeloid Leukemia Progression
title Runt-Related Transcription Factor 3 Promotes Acute Myeloid Leukemia Progression
title_full Runt-Related Transcription Factor 3 Promotes Acute Myeloid Leukemia Progression
title_fullStr Runt-Related Transcription Factor 3 Promotes Acute Myeloid Leukemia Progression
title_full_unstemmed Runt-Related Transcription Factor 3 Promotes Acute Myeloid Leukemia Progression
title_short Runt-Related Transcription Factor 3 Promotes Acute Myeloid Leukemia Progression
title_sort runt-related transcription factor 3 promotes acute myeloid leukemia progression
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8549545/
https://www.ncbi.nlm.nih.gov/pubmed/34722267
http://dx.doi.org/10.3389/fonc.2021.725336
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