DEPDC1 is required for cell cycle progression and motility in nasopharyngeal carcinoma.
DEPDC1 is required for cell cycle progression and motility in nasopharyngeal carcinoma.
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DEPDC1 是鼻咽癌细胞周期进展和运动所必需的
DOI：
10.18632/oncotarget.18868
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发表时间：
2017-09-08
期刊：
影响因子：
--
通讯作者：
Bu Y
中科院分区：
文献类型：
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作者：
Feng X;Zhang C;Zhu L;Zhang L;Li H;He L;Mi Y;Wang Y;Zhu J;Bu Y
DEP domain containing 1（DEPDC 1）是一个新发现的与肿瘤和细胞周期相关的基因，已被证明是膀胱癌治疗的新靶点。然而，DEPDC 1在鼻咽癌（NPC）中的功能参与和治疗潜力仍不清楚。我们的研究结果表明，DEPDC 1在mRNA和蛋白质水平上在NPC组织中比正常或非肿瘤组织中过表达。siRNA介导的DEPDC 1耗竭导致NPC细胞系CNE-1和HNE-1的增殖显著抑制和细胞周期进展延迟。间接免疫荧光分析的详细分析表明，DEPDC 1耗尽引起显着的有丝分裂阻滞伴随有丝分裂缺陷，如多极纺锤体和多个细胞核，然后凋亡细胞死亡。值得注意的是，DEPDC 1消耗也降低了两种细胞系的迁移和侵袭能力。与其在NF-κB途径中的调节作用一致，DEPDC 1的敲除导致A20显着上调，并导致与增殖和肿瘤发生（c-Myc、BCL 2、CCND 1、CCNB 1和CCNB 2）以及转移（MMP 2、MMP 9、ICAM 1、vimentin、Twist 1）有关的多个NF-κB下游靶基因下调。此外，体内研究表明，DEPDC 1敲低也引起NPC异种移植裸鼠模型中肿瘤生长的显著抑制。综上所述，我们目前的研究表明，DEPDC 1在NPC细胞中基本上是加速细胞周期进程和运动所必需的，并强烈建议DEPDC 1可能作为NPC的新的治疗靶点。
DEP domain containing 1 (DEPDC1) is a newly identified cancer-related and cell cycle related gene and has been demonstrated as a novel therapeutic target for bladder cancer. However, the functional involvement and therapeutic potential of DEPDC1 in nasopharyngeal carcinoma (NPC) remains unclear. Our results showed that DEPDC1 was overexpressed at both mRNA and protein levels in NPC tissues compared with normal or non-tumor tissues. The siRNA-mediated DEPDC1 depletion resulted in significant inhibition of proliferation and delay in cell cycle progression in both NPC cell lines, CNE-1 and HNE-1. Detailed analysis with indirect immunofluorescence assays revealed that DEPDC1 depletion caused significant mitotic arrest accompanied with mitotic defects such as multipolar spindles and multiple nuclei followed by apoptotic cell death. Notably, DEPDC1 depletion also reduces migration and invasion ability in both cell lines. Consistent with its regulatory role in NF-κB pathway, knockdown of DEPDC1 caused significant upregulation of A20 and downregulation of mutiple NF-κB downstream target genes implicated in proliferation and tumorigenesis (c-Myc, BCL2, CCND1, CCNB1 and CCNB2), and metastasis (MMP2, MMP9, ICAM1, vimentin, Twist1). Moreover, in vivo study demonstrated that DEPDC1 knockdown also caused significant inhibition of tumor growth in the NPC xenograft nude mouse model. Taken together, our present study demonstrated that DEPDC1 is essentially required for the accelerated cell cycle progression and motility in NPC cells, and strongly suggested that DEPDC1 may serve as a novel therapeutic target in NPC.