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KMID : 0620920210530121902
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Experimental & Molecular Medicine
2021 Volume.53 No. 12 p.1902 ~ p.1910
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Epigenetic silencing of UBXN8 contributes to leukemogenesis in t(8;21) acute myeloid leukemia
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Yang Erna
Guan Wei
Gong Desheng
Li Jieying
Han Caixia
Zhang Juan
Wang Hong
Kang Synat
Gao Xuefeng
Li Yonghui
Yu Li
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Abstract
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The formation of the RUNX1-RUNX1T1 fusion protein, resulting from the t(8;21) translocation, is considered to be one of the initiating events of t(8;21) acute myeloid leukemia (AML). However, the mechanisms of the oncogenic mechanism of RUNX1-RUNX1T1 remain unclear. In this study, we found that RUNX1-RUNX1T1 triggers the heterochromatic silencing of UBXN8 by recognizing the RUNX1-binding sites and recruiting chromatin-remodeling enzymes to the UBXN8 promoter region. Decitabine, a specific inhibitor of DNA methylation, upregulated the expression of UBXN8 in RUNX1-RUNX1T1+ AML cell lines. Overexpression of UBXN8 inhibited the proliferation and colony-forming ability of and promoted cell cycle arrest in t(8;21) AML cell lines. Enhancing UBXN8 levels can significantly inhibit tumor proliferation and promote the differentiation of RUNX1-RUNX1T1+ cells in vivo. In conclusion, our results indicated that epigenetic silencing of UBXN8 via methylation of its promoter region mediated by the RUNX1-RUNX1T1 fusion protein contributes to the leukemogenesis of t(8;21) AML and that UBXN8 targeting may be a potential therapeutic strategy for t(8;21) AML.
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KEYWORD
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Acute myeloid leukaemia, Tumour heterogeneity
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