Up-regulated A20 promotes proliferation, regulates cell cycle progression and induces chemotherapy resistance of acute lymphoblastic leukemia cells
Up-regulated A20 promotes proliferation, regulates cell cycle progression and induces chemotherapy resistance of acute lymphoblastic leukemia cells
复制标题
上调 A20 促进急性淋巴细胞白血病细胞增殖、调节细胞周期进程并诱导化疗耐药
DOI：
10.1016/j.leukres.2015.06.004
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发表时间：
2015-09-01
影响因子：
2.7
通讯作者：
Wang, Jianxiang
中科院分区：
文献类型：
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作者：
Chen, Shuying;Xing, Haiyan;Wang, Jianxiang
A20，也称为肿瘤坏死因子-α（TNF α）诱导蛋白3（TNFAIP 3），已被鉴定为许多实体瘤中细胞存活的关键调节因子。然而，关于A20在急性淋巴细胞白血病（ALL）中的蛋白表达水平和功能知之甚少。在这项研究中，我们发现A20在ALL患者和几种细胞系中上调。Jurkat、Nalm-6和Reh细胞中A20的敲低导致细胞增殖减少，这与细胞周期停滞相关。A20基因敲低细胞中磷酸化ERK（p-ERK）表达下调，而p53和p21表达上调。此外，A20敲低诱导Jurkat和Reh细胞凋亡，并增强这些细胞系对化疗药物的敏感性。这些结果表明，A20可能通过调节细胞周期进程来刺激细胞增殖。A20抑制某些类型的ALL细胞的凋亡，从而增强其对化疗的抵抗力。这种效应通过A20沉默而消除。这些结果表明，A20可能有助于ALL的发病机制，它可能被用作ALL治疗的新靶点。(C)2015爱思唯尔有限公司版权所有。
A20, also known as tumor necrosis factor-alpha (TNF alpha)-induced protein 3 (TNFAIP3), has been identified as a key regulator of cell survival in many solid tumors. However, little is known about the protein expression level and function of A20 in acute lymphoblastic leukemia (ALL). In this study, we found that A20 is up-regulated in ALL patients and several cell lines. Knockdown of A20 in Jurkat, Nalm-6, and Reh cells resulted in reduced cell proliferation, which was associated with cell cycle arrest. Phospho-ERK (p-ERK) was also down-regulated, while p53 and p21 were up-regulated in A20 knockdown cells. In addition, A20 knockdown induced apoptosis in Jurkat and Reh cells and enhanced the sensitivity of these cell lines to chemotherapeutic drugs. These results indicate that A20 may stimulate cell proliferation by regulating cell cycle progression. A20 inhibited apoptosis in some types of ALL cells, thereby enhancing their resistance to chemotherapy. This effect was abolished through A20 silencing. These findings suggest that A20 may contribute to the pathogenesis of ALL and that it may be used as a new therapeutic target for ALL treatment. (C) 2015 Elsevier Ltd. All rights reserved.