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超级增强子相关基因 CAPG 促进 AML 进展。

Super-enhancer-associated gene CAPG promotes AML progression.

机构信息

Department of Clinical Laboratory, Peking University First Hospital, Beijing, China.

Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.

出版信息

Commun Biol. 2023 Jun 9;6(1):622. doi: 10.1038/s42003-023-04973-1.

Abstract

Acute myeloid leukemia is the most common acute leukemia in adults, the barrier of refractory and drug resistance has yet to be conquered in the clinical. Abnormal gene expression and epigenetic changes play an important role in pathogenesis and treatment. A super-enhancer is an epigenetic modifier that promotes pro-tumor genes and drug resistance by activating oncogene transcription. Multi-omics integrative analysis identifies the super-enhancer-associated gene CAPG and its high expression level was correlated with poor prognosis in AML. CAPG is a cytoskeleton protein but has an unclear function in AML. Here we show the molecular function of CAPG in regulating NF-κB signaling pathway by proteomic and epigenomic analysis. Knockdown of Capg in the AML murine model resulted in exhausted AML cells and prolonged survival of AML mice. In conclusion, SEs-associated gene CAPG can contributes to AML progression through NF-κB.

摘要

急性髓细胞白血病是成人中最常见的急性白血病,临床尚未克服难治性和耐药性的障碍。异常基因表达和表观遗传变化在发病机制和治疗中起着重要作用。超级增强子是一种表观遗传修饰物,通过激活致癌基因转录促进肿瘤基因和耐药性。多组学整合分析确定了超级增强子相关基因 CAPG,其高表达水平与 AML 的不良预后相关。CAPG 是一种细胞骨架蛋白,但在 AML 中的功能尚不清楚。在这里,我们通过蛋白质组学和表观基因组学分析显示了 CAPG 在调节 NF-κB 信号通路中的分子功能。在 AML 小鼠模型中敲低 Capg 导致耗尽的 AML 细胞,并延长 AML 小鼠的存活时间。总之,SE 相关基因 CAPG 可以通过 NF-κB 促进 AML 的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/971a/10256737/914a0c182c66/42003_2023_4973_Fig1_HTML.jpg

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