期刊
FRONTIERS IN ONCOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.725336
关键词
RUNX3; super-enhancer; acute myeloid leukemia; cell cycle; apoptosis; DNA repair
类别
资金
- National Natural Science Foundation of China [NSFC 81700149, NSFC 81870127]
- Sanming Project of Medicine in Shenzhen [SZSM201911004]
- Sun Yat-sen University [ZSQYRSFPD0017]
In this study, it was found that RUNX3 is a super-enhancer-associated gene highly expressed in AML cells, and its high expression is associated with poor prognosis in AML patients. Knockdown of Runx3 significantly inhibits leukemia progression by inducing DNA damage and apoptosis.
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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