Oncotarget

Research Papers:

DEPDC1 is required for cell cycle progression and motility in nasopharyngeal carcinoma

Xuefei Feng, Chundong Zhang, Ling Zhu, Lian Zhang, Hongxia Li, Longxia He, Yan Mi, Yitao Wang, Jiang Zhu _ and Youquan Bu

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Oncotarget. 2017; 8:63605-63619. https://doi.org/10.18632/oncotarget.18868

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Abstract

Xuefei Feng1,*, Chundong Zhang2,*, Ling Zhu1, Lian Zhang2, Hongxia Li1, Longxia He1, Yan Mi1, Yitao Wang2, Jiang Zhu1 and Youquan Bu2

1Department of Otolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China

2Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, China

*These authors have contributed equally to this work

Correspondence to:

Jiang Zhu, email: [email protected]

Youquan Bu, email: [email protected], [email protected]

Keywords: DEPDC1, cell cycle, mitosis, nasopharyngeal carcinoma

Received: January 09, 2017    Accepted: June 02, 2017    Published: June 29, 2017

ABSTRACT

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.


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