β-TrCP1 promotes cell proliferation via TNF-dependent NF-κB activation in diffuse large B cell lymphoma

β-TrCP1 promotes cell proliferation via TNF-dependent NF-κB activation in diffuse large B cell lymphoma
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beta-TrCP1 通过 TNF 依赖性 NF-κ B 激活促进弥漫性大 B 细胞淋巴瘤细胞增殖

DOI:
10.1080/15384047.2019.1683332
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发表时间:
2019-11-18
影响因子:
3.6
通讯作者:
He, Song
He, Song
中科院分区:
医学3区
文献类型:
--
作者:
Cai, Nannan;Chen, Zhuolin;He, Song

文献摘要

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弥漫性大B细胞淋巴瘤(DLBCL)是B细胞非霍奇金淋巴瘤中最常见的一种类型,是一组异质性浸润性疾病。其发生机制与NF-κ B B的组成性激活密切相关。本研究旨在探讨β-TRCP 1在DLBCL中的作用及其机制。CCK-8和EdU检测显示,β-TRCP 1在TNF-α刺激下可促进DLBCL细胞的生长。此外,β-TRCP 1的过表达增强了TNF α存在时NF-κ B的激活。此外,β-TRCP 1的异位表达降低I κ B-α表达,但增加磷酸化p65表达。此外,β-TRCP 1通过加速G1-S期转变促进细胞周期进程。我们还发现,沉默β-TrCP 1增加米托蒽醌诱导的细胞生长停滞和凋亡。基于这些,我们提出β-TRCP 1的表达通过DLBCL细胞中TNF依赖性NF-κ B活化促进细胞增殖。
Diffuse large B cell lymphoma (DLBCL), a heterogeneous group of invasive disease, is the most common type of B-cell non-Hodgkin's lymphomas. The mechanism of its development is closely related to the constitutive activation of NF-kappa B. In this study, we investigated the function and the mechanism of beta-TRCP1 in DLBCL. CCK8 and EdU assays showed that beta-TRCP1 could promote the growth of DLBCL cells under the stimulation of TNF alpha. Furthermore, overexpression of beta-TRCP1 enhanced NF-kappa B activation in the presence of TNF alpha. Moreover, ectopic expression of beta-TRCP1 decreased I kappa B-alpha expression but increased phospho-p65 expression. In addition, beta-TRCP1 promoted cell cycle progression by accelerating G1-S phase transition. We also found that silencing of beta-TrCP1 increased mitoxantrone-induced cell growth arrest and apoptosis. Based on these, we proposed that the expression of beta-TRCP1 promoted cell proliferation via TNF-dependent NF-kappa B activation in DLBCL cells.