Zhang Wenwen, Ma Qian, Long Bing, Sun Zhangyi, Liu Lingling, Lin Dongjun, Zhao Minyi
Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, ShenZhen, China.
Key Laboratory of Stem Cells and Tissue Engineering, Zhongshan School of Medicine, Sun Yat-sen University, Ministry of Education, Guangzhou, China.
Front Oncol. 2021 Oct 12;11:725336. doi: 10.3389/fonc.2021.725336. eCollection 2021.
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 was a super-enhancer-associated gene and highly expressed in AML cells. The Cancer Genome Atlas (TCGA) database showed high expression of correlated with poor prognosis of AML patients. We observed that 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. knockdown obviously inhibited the expression of these genes in AML cells. Overall, we identified as an oncogene overexpressed in AML cells, and knockdown suppressed AML progression by inducing DNA damage and apoptosis.
急性髓系白血病（AML）是一种侵袭性血液系统恶性肿瘤，复发/难治率高。遗传和表观遗传异常是白血病发生的驱动因素。来自Runt相关转录因子（RUNX）家族的RUNX1和RUNX2在AML发病机制中起重要作用。然而，RUNX3与AML之间的关系仍不清楚。在此，我们发现[基因名称]是一个与超级增强子相关的基因，在AML细胞中高表达。癌症基因组图谱（TCGA）数据库显示，[基因名称]的高表达与AML患者的不良预后相关。我们观察到，[基因名称]敲低通过诱导DNA损伤增强小鼠AML细胞凋亡，显著抑制白血病进展。通过染色质免疫沉淀测序（ChIP-seq）分析，我们发现与正常骨髓细胞相比，AML细胞中的RUNX3主要结合更多参与DNA损伤修复和抗凋亡途径的基因。[基因名称]敲低明显抑制AML细胞中这些基因的表达。总体而言，我们确定[基因名称]为AML细胞中过表达的癌基因，并通过诱导DNA损伤和凋亡抑制AML进展。
