Feng Xuefei, Zhang Chundong, Zhu Ling, Zhang Lian, Li Hongxia, He Longxia, Mi Yan, Wang Yitao, Zhu Jiang, Bu Youquan
Department of Otolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, China.
Oncotarget. 2017 Jun 29;8(38):63605-63619. doi: 10.18632/oncotarget.18868. eCollection 2017 Sep 8.
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, 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.
含DEP结构域蛋白1（DEPDC1）是一个新发现的与癌症及细胞周期相关的基因，已被证明是膀胱癌的一个新治疗靶点。然而，DEPDC1在鼻咽癌（NPC）中的功能作用和治疗潜力仍不清楚。我们的结果显示，与正常或非肿瘤组织相比，NPC组织中DEPDC1在mRNA和蛋白水平均过表达。在两种NPC细胞系CNE-1和HNE-1中，siRNA介导的DEPDC1缺失导致细胞增殖显著抑制及细胞周期进程延迟。间接免疫荧光分析的详细结果显示，DEPDC1缺失导致显著的有丝分裂停滞，并伴有有丝分裂缺陷，如多极纺锤体和多核，随后是凋亡性细胞死亡。值得注意的是，DEPDC1缺失也降低了两种细胞系的迁移和侵袭能力。与其在NF-κB通路中的调节作用一致，DEPDC1敲低导致A20显著上调，以及多个与增殖和肿瘤发生（c-Myc、BCL2、CCND1、CCNB1和CCNB2）及转移（MMP2、MMP9、ICAM1、波形蛋白、Twist1）相关的NF-κB下游靶基因下调。此外，研究表明DEPDC1敲低在NPC异种移植裸鼠模型中也导致肿瘤生长显著抑制。综上所述，我们目前的研究表明，DEPDC1是NPC细胞加速细胞周期进程和运动所必需的，强烈提示DEPDC1可能作为NPC的一个新治疗靶点。
