p53 suppression is essential for oncogenic SPAG5 upregulation in lung adenocarcinoma
p53 suppression is essential for oncogenic SPAG5 upregulation in lung adenocarcinoma
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p53 抑制对于肺腺癌中致癌性 SPAG5 上调至关重要
DOI：
10.1016/ibbrc.2019.03.198
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发表时间：
2019-05-28
影响因子：
3.1
通讯作者：
Deng, Jiong
中科院分区：
文献类型：
--
作者：
Wang, Tong;Li, Kaimi;Deng, Jiong
精子相关抗原5（SPAG 5）的异常表达在几种类型的癌症中起致癌作用。然而，SPAG 5在肺腺癌中的功能尚不清楚。在这项研究中，我们研究了SPAG 5在肺腺癌中的作用。我们发现SPAG 5在大多数肺腺癌细胞系中与正常肺上皮细胞相比上调。SPAG 5基因敲减抑制肺腺癌A549细胞的增殖、集落形成和迁移，并抑制体内肿瘤生长。这些表明上调的SPAG 5促进肺肿瘤进展。重要的是，用MDM 2抑制剂Nutlin-3a治疗恢复了野生型p53肺腺癌细胞A549和H460中p53和p21的表达，并抑制了SPAG 5的表达，但在p53缺失的肺癌细胞H1299中没有。这表明p53信号通路对于SPAG 5抑制是必不可少的。此外，在A549和H460细胞中敲低p53或p21减弱了Nutlin-3a诱导的SPAG 5抑制，这进一步支持了SPAG 5抑制需要p53-p21轴。因此，SPAG 5可以作为一个预后标志物，靶向p53-p21-SPAG 5轴的治疗策略可能具有重要的临床意义。(C)2019爱思唯尔公司All rights reserved.
Aberrant expression of sperm-associated antigen 5 (SPAG5) is implicated to play oncogenic roles in several types of cancers. However, the functions of SPAG5 in lung adenocarcinoma remain unclear. In this study, we investigated the role of SPAG5 in lung adenocarcinoma. We found that SPAG5 was upregulated in most of the lung adenocarcinoma cell lines as compared to normal lung epithelial cells. SPAG5 knockdown suppressed proliferation, colony forming, and migration of lung adenocarcinoma A549 cells in vitro and inhibited tumor growth in vivo. These suggest that upregulated SPAG5 promotes lung tumor progression. Importantly, treatment with MDM2 inhibitor, Nutlin-3a, restored p53 and p21 expression and suppressed SPAG5 expression in wild-type p53 lung adenocarcinoma cells, A549 and H460, but not in p53-null lung cancer cells, H1299. This suggests that the p53 signal pathway is essential for SPAG5 suppression. In addition, knocking-down p53 or p21 in A549 and H460 cells attenuated Nutlin-3a-induced repression of SPAG5, which further supports that the p53-p21 axis is required for SPAG5 repression. Thus, SPAG5 can serve as a prognostic marker, and therapeutic strategy targeting the p53-p21-SPAG5 axis may have important clinical implications. (C) 2019 Elsevier Inc. All rights reserved.