Nasopharyngeal carcinoma (NPC) is a common malignant carcinoma of the head and neck, and the biological mechanisms underlying the pathogenesis of NPC remain not fully understood. In the present study, we systematically analyzed four independent NPC transcriptomic datasets and focused on identifying the critical molecular networks and novel key hub genes implicated in NPC. We found totally 170 common overlapping differentially expressed genes (DEGs) in the four NPC datasets. GO and KEGG pathway analysis revealed that cell cycle dysregulation is a critical event in NPC. Protein–protein interaction (PPI) network analysis identified a 15 hub-gene core network with overexpressed kinesin family member 2C (KIF2C) as a central regulator. Loss-of-function study demonstrated that knockdown of KIF2C significantly inhibited cell growth and cell motility, and delayed cell cycle progression, accompanied with dramatic mitotic defects in spindle formation in NPC cells. RNA-seq analysis revealed that KIF2C knockdown led to deregulation of various downstream genes. KIF2C could also regulate the AKT/mTOR pathways, and enhance paclitaxel sensitivity in NPC cells. Taken together, our results suggest that cell cycle dysregulation is a critical event during NPC pathogenesis and KIF2C is a novel key mitotic hub gene with therapeutic potential in NPC.

鼻咽癌（NPC）是一种常见的头颈部恶性肿瘤，其发病机制的生物学机制尚不完全清楚。在本研究中，我们系统地分析了四个独立的 NPC 转录组数据集，并专注于识别与 NPC 相关的关键分子网络和新的关键枢纽基因。我们在四个 NPC 数据集中发现了总共 170 个常见的重叠差异表达基因 (DEG)。GO 和 KEGG 通路分析显示细胞周期失调是 NPC 中的一个关键事件。蛋白质-蛋白质相互作用 (PPI) 网络分析确定了一个由 15 个中枢基因组成的核心网络，其中过度表达的驱动蛋白家族成员 2C (KIF2C) 作为中央调节器。功能丧失研究表明，KIF2C 的敲低显着抑制细胞生长和细胞运动，和延迟的细胞周期进程，伴随着 NPC 细胞中纺锤体形成的显着有丝分裂缺陷。RNA-seq 分析表明，KIF2C 敲低导致各种下游基因失调。KIF2C 还可以调节 AKT/mTOR 通路，并增强 NPC 细胞对紫杉醇的敏感性。综上所述，我们的结果表明细胞周期失调是 NPC 发病机制中的一个关键事件，而 KIF2C 是一种在 NPC 中具有治疗潜力的新型关键有丝分裂中枢基因。