Huang Pan, Hu Yi-Dou, Liu Yuan-Jie, Li Jie-Pin, Zhang Yong-Hua
Department of Oncology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, 215600, People's Republic of China.
No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People's Republic of China.
J Hepatocell Carcinoma. 2023 Jun 22;10:959-978. doi: 10.2147/JHC.S417501. eCollection 2023.
The nuclear pore complex (NPC) is the main mediator of nuclear and cytoplasmic communication, and delaying or blocking nuclear RNA export and protein shuttling can inhibit cell proliferation and induce apoptosis. Although NPC is a research hotspot in structural biology, relevant studies in hepatocellular carcinoma are scarce, especially in terms of translation into clinical practice.
This study used a bioinformatics approach combining validation experiments to investigate the biological mechanisms that may be related with NPC. A series of experiments performed to explore the function of the Targeting protein for Xenopus kinesin-like protein 2 (TPX2) in HCC.
Patients with HCC can be divided into two NPC clusters. Patients with high NPC levels (C1) had a shorter survival time than those with low NPC levels (C2) and are characterised by high levels of proliferative signals. We demonstrated that TPX2 regulates HCC growth and inhibits apoptosis in an NPC-dependent manner and contributes to the maintenance of HCC stemness. We developed the NPCScore to predict the prognosis and degree of differentiation in HCC patients.
NPC plays an important role in the malignant proliferation of HCC. Assessing NPC expression patterns could help enhance our understanding of tumor cell proliferation and could guide more effective chemotherapeutic strategies.
核孔复合体(NPC)是核质通讯的主要介质,延迟或阻断核RNA输出和蛋白质穿梭可抑制细胞增殖并诱导凋亡。尽管NPC是结构生物学的研究热点,但在肝细胞癌方面的相关研究较少,尤其是在转化为临床实践方面。
本研究采用生物信息学方法结合验证实验来探究可能与NPC相关的生物学机制。进行了一系列实验以探索靶向蛋白Xenopus驱动蛋白样蛋白2(TPX2)在肝癌中的功能。
肝癌患者可分为两个NPC簇。NPC水平高的患者(C1)比NPC水平低的患者(C2)生存时间短,且具有高水平的增殖信号特征。我们证明TPX2以NPC依赖的方式调节肝癌生长并抑制凋亡,并有助于维持肝癌干性。我们开发了NPCScore来预测肝癌患者的预后和分化程度。
NPC在肝癌的恶性增殖中起重要作用。评估NPC表达模式有助于增强我们对肿瘤细胞增殖的理解,并可指导更有效的化疗策略。