HBx integration in diffuse large B-cell lymphoma inhibits Caspase-3-PARP related apoptosis

IF 4.7 Q1 VIROLOGY Tumour Virus Research Pub Date : 2024-07-18 DOI:10.1016/j.tvr.2024.200290
Yanchun Wang , Xiaolin Guan , Fangfang Lv , Yi Rong , Xin Meng , Ying Tong , Xiaolu Ma , Hui Zheng , Cuncun Chen , Suhong Xie , Heng Zhang , Feng Dong , Lin Guo , Renquan Lu
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Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common pathological type of non-Hodgkin lymphoma, and is closely associated with hepatitis B virus (HBV) infection status and hepatitis B X (HBx) gene integration. This project investigated the cellular biological effects and molecular mechanisms responsible for lymphomagenesis and the progression of HBx integration in DLBCL. The data showed that clinical DLBCL cells demonstrated HBx integration, and the sequencing analysis of integrated sites validated HBx integration in the constructed HBx-transfected cells. Compared with control cells, HBx-transfected cells had a significantly reduced proportion of mitochondrial membrane potential, signals of chromosomal DNA breaks, and proportion of apoptotic cells. Further studies found that this decreased apoptosis level was associated with a significant reduction of cleaved Caspase-3 and downstream poly ADP-ribose polymerase (PARP) proteins, revealing the molecular mechanisms of HBx-associated apoptosis in DLBCL. Animal experiments also demonstrated that the protein expression of cleaved Caspase-3 and PARP was prominently reduced in HBx-transfected cells from subcutaneous tumors in mice. Furthermore, the HBx-integrated cells in clinical tissues had significantly lower cleaved PARP levels than the HBx-negative samples. Therefore, HBx integration inhibits cell apoptosis through the Caspase-3-PARP pathway in DLBCL indicating a potential biomarker and therapeutic target in HBV related DLBCL.

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弥漫大 B 细胞淋巴瘤中的 HBx 整合可抑制与 Caspase-3-PARP 相关的细胞凋亡。
弥漫大B细胞淋巴瘤(DLBCL)是非霍奇金淋巴瘤中最常见的病理类型,与乙型肝炎病毒(HBV)感染状态和乙型肝炎X(HBx)基因整合密切相关。该项目研究了 DLBCL 中淋巴瘤发生和 HBx 整合进展的细胞生物学效应和分子机制。数据显示,临床 DLBCL 细胞表现出 HBx 整合,整合位点的测序分析验证了 HBx 整合在构建的 HBx 转染细胞中。与对照细胞相比,HBx转染细胞的线粒体膜电位比例、染色体DNA断裂信号和凋亡细胞比例均显著降低。进一步研究发现,细胞凋亡水平的降低与裂解的Caspase-3和下游聚ADP-核糖聚合酶(PARP)蛋白的显著减少有关,揭示了HBx相关DLBCL细胞凋亡的分子机制。动物实验也表明,在小鼠皮下肿瘤的 HBx 转染细胞中,Caspase-3 和 PARP 的蛋白表达显著减少。此外,临床组织中的 HBx 整合细胞的裂解 PARP 水平明显低于 HBx 阴性样本。因此,HBx整合通过Caspase-3-PARP途径抑制DLBCL中的细胞凋亡,这表明HBV相关DLBCL是一种潜在的生物标记物和治疗靶点。
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来源期刊
Tumour Virus Research
Tumour Virus Research Medicine-Infectious Diseases
CiteScore
6.50
自引率
2.30%
发文量
16
审稿时长
56 days
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