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DEPDC1 is required for cell cycle progression and motility in nasopharyngeal carcinoma
Xuefei Feng1, Chundong Zhang2, Ling Zhu1
1Department of Otolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
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.
Insights
DEP domain containing 1 (DEPDC1) is overexpressed in nasopharyngeal carcinoma (NPC). Depleting DEPDC1 inhibits NPC cell proliferation, migration, and invasion, suggesting it as a potential therapeutic target for NPC.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- DEP domain containing 1 (DEPDC1) is a novel cancer-related gene and a potential therapeutic target for bladder cancer.
- The role of DEPDC1 in nasopharyngeal carcinoma (NPC) remains largely unknown.
- Understanding DEPDC1's function in NPC is crucial for developing new treatment strategies.
Purpose of the Study:
- To investigate the functional involvement of DEPDC1 in nasopharyngeal carcinoma (NPC).
- To evaluate the therapeutic potential of targeting DEPDC1 in NPC.
- To elucidate the molecular mechanisms underlying DEPDC1's role in NPC progression.
Main Methods:
- Quantitative real-time PCR and Western blotting to assess DEPDC1 expression in NPC tissues and cell lines.
- siRNA-mediated DEPDC1 depletion to study its effects on NPC cell proliferation, cell cycle, migration, and invasion.
- Indirect immunofluorescence assays to analyze mitotic defects.
- Analysis of NF-κB pathway signaling components and downstream target genes.
- In vivo studies using NPC xenograft nude mouse models.
Main Results:
- DEPDC1 was significantly overexpressed in NPC tissues compared to normal tissues.
- DEPDC1 depletion inhibited NPC cell proliferation, induced cell cycle arrest, and promoted apoptosis.
- Knockdown of DEPDC1 reduced NPC cell migration and invasion.
- DEPDC1 knockdown modulated the NF-κB pathway, affecting key genes involved in proliferation, tumorigenesis, and metastasis.
- In vivo studies confirmed that DEPDC1 knockdown inhibited tumor growth in NPC xenografts.
Conclusions:
- DEPDC1 is essential for cell cycle progression and motility in NPC cells.
- DEPDC1 plays a significant role in NPC tumorigenesis and metastasis.
- DEPDC1 represents a promising novel therapeutic target for nasopharyngeal carcinoma.
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