Expression and regulation of COP1 in chronic lymphocytic leukemia cells for promotion of cell proliferation and tumorigenicity
Expression and regulation of COP1 in chronic lymphocytic leukemia cells for promotion of cell proliferation and tumorigenicity
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COP1在慢性淋巴细胞白血病细胞中的表达和调节促进细胞增殖和致瘤性。
DOI：
10.3892/or.2015.4526
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发表时间：
2016-03-01
期刊：
影响因子：
4.2
通讯作者：
Xu, Kailin
中科院分区：
文献类型：
--
作者：
Fu, Chunling;Gong, Yanqing;Xu, Kailin
慢性淋巴细胞白血病（Chronic lymphocytic leukemia， CLL）是西方国家最常见的一种白血病，主要源于细胞增殖和凋亡失调引起的异常B细胞积聚。CLL细胞中增殖相关基因的畸变导致细胞停滞在G0/G1期，或一小部分细胞快速生长，使CLL的发病机制进一步复杂化。组成型光形态形成1 （COP1）作为E3泛素连接酶，参与哺乳动物细胞的许多生物学过程，但其在慢性淋巴细胞白血病（CLL）进展中的作用尚不清楚。在本研究中，我们分析了23名CLL患者和3名健康供者外周血单个核细胞（PBMCs）中COP1的表达。CLL患者COP1表达上调与CLL临床分期和ZAP-70表达呈正相关，与del（13q14）和del（17q-）呈正相关。过表达COP1可显著促进细胞集落的形成和增殖，特别是通过抑制fox01和p21促进s期细胞的积累。此外，COP1的过表达加速了HG3细胞的致瘤性，促进了异种移植物的生长。因此，本研究揭示了COP1在CLL细胞增殖和致瘤性中起重要作用，可能是慢性淋巴细胞白血病过程的有用指标。
Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, and mainly originates from an accumulation of abnormal B cells caused by the dysregulation of cell proliferation and apoptosis. The aberration of proliferation-related gene in CLL cells induces cell arrest at G0/G1 phase, or a small section shows rapid cell growth, which further complicates the pathogenesis of CLL. The constitutively photomorphogenic 1 (COP1), as an E3 ubiquitin ligase, is involved in many biological processes in mammalian cells, but its role in chronic lymphocytic leukemia (CLL) progression remains unclear. In the present study, we analyzed the expression of COP1 in peripheral blood mononuclear cells (PBMCs) from 23 CLL patients and 3 healthy donors. The observed upregulated expression of COP1 in CLL patients was positively correlated with CLL clinical stage and ZAP-70 expression, but not del(13q14) and del(17q-). Overexpression of COP1 significantly promoted cell colony formation and proliferation, especially contributing to the accumulation of cells in S-phase by inhibition of FoxO1 and p21. Moreover, overexpression of COP1 accelerated tumorigenicity of HG3 cells and promoted xenograft growth. Therefore, the present study revealed that COP1 plays an important role in CLL cell proliferation and tumorigenicity, and may be a useful indicator of the chronic lymphocytic leukemia processes.