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The c-Rel-c-Myc axis controls metabolism and proliferation of human T leukemia cells.
Molecular Immunology ( IF 3.6 ) Pub Date : 2020-07-10 , DOI: 10.1016/j.molimm.2020.06.029
Xinyuan Li 1 , George Luo 1 , Ting Li 1 , Honghong Sun 1 , Wei Wang 1 , Emily Eiler 1 , Jason R Goldsmith 1 , Youhai H Chen 1
Affiliation  

Genome-wide association studies have established that human REL is a susceptibility gene for lymphoid cancers and inflammatory diseases. REL is the hematopoietic member of the nuclear factor-κB (NF-κB) family and is frequently amplified in human lymphomas. However, the mechanism through which REL and its encoded protein c-Rel affect human lymphoma is largely unknown. Using both loss-of-function and gain-of-function approaches, we studied the roles of REL gene in human Jurkat leukemia cells. Compared with control Jurkat cells, REL knockout cells exhibited significant defects in cell growth and mitochondrial respiration. Genome-wide transcriptome analyses revealed that T cells lacking c-Rel had selective defects in the expression of inflammatory and metabolic genes including c-Myc. We found that c-Rel controlled the expression of c-Myc through its promotor, and expressing c-Myc in c-Rel-deficient lymphoma cells rescued their proliferative and metabolic defects. Thus, the human c-Rel-c-Myc axis controls lymphoma growth and metabolism and could be a therapeutic target for lymphomas.



中文翻译:

c-Rel-c-Myc 轴控制人 T 白血病细胞的代谢和增殖。

全基因组关联研究已确定人类REL是淋巴癌和炎症性疾病的易感基因。REL是核因子-κB (NF-κB) 家族的造血成员,在人类淋巴瘤中经常扩增。然而, REL及其编码蛋白 c-Rel 影响人类淋巴瘤的机制尚不清楚。使用功能丧失和功能获得方法,我们研究了REL基因在人 Jurkat 白血病细胞中的作用。与对照 Jurkat 细胞相比,REL敲除细胞在细胞生长和线粒体呼吸方面表现出显着缺陷。全基因组转录组分析显示,缺乏 c-Rel 的 T 细胞在包括 c-Myc 在内的炎症和代谢基因的表达方面存在选择性缺陷。我们发现c-Rel通过其启动子控制c-Myc的表达,并且在c-Rel缺陷的淋巴瘤细胞中表达c-Myc可以挽救其增殖和代谢缺陷。因此,人类 c-Rel-c-Myc 轴控制淋巴瘤的生长和代谢,并可能成为淋巴瘤的治疗靶点。

更新日期:2020-07-10
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