肝细胞癌(HCC)是原发性肝癌最常见的类型，致死率极高。1q21.1–32.1染色体区域扩增在HCC患者中的发生频率最高，且与HCC早期发生密切相关。核孔复合物蛋白TPR位于DNA拷贝数扩增的高频区1q31.1，作为支架元件调节胞核–胞浆之间的蛋白质和mRNAs运输，而TPR在HCC中的作用及相关分子机制仍不清楚。我们初步研究发现，TPR在肝癌组织中的表达显著高于癌旁组织，其表达水平与肿瘤大小及病人预后显著相关；下调TPR表达，能够抑制肝癌细胞活力，促进细胞凋亡和衰老；TPR的在HCC中高表达受Hippo信号通路下游转录因子YAP/TEAD1调控；TPR促进HCC发展可能与线粒体功能有关。本课题将进一步明确TPR在肝癌中高表达的调控机理，从胞核–胞浆物质转运的角度深入研究TPR促进肝癌发生发展的具体分子机制，为改善HCC的诊疗提供新思路和干预靶点。

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and is one of the most fatal disease in China. Gain of chromosome 1q21.1–32.1 is the most frequent amplifying region in HCC, and is closely associated with hepatocarcinogenesis. Nuclear pore complex-associated protein TPR is located in recurrently altered region 1q31.1. TPR functions as a scaffolding element essential for normal nucleocytoplasmic transport of proteins and mRNAs. However, molecular and cellular mechanisms underlying the role of TPR in HCC remain unclear. Our preliminary studies revealed that TPR expression was significantly increased in HCC tissue compared to paracancerous tissue, and the expression level of TPR was closely correlated with tumor size and prognosis of patients with HCC. Downregulation of TPR with siRNA significantly inhibited the cell viability while promoted cell apoptosis and senescence. Afterwards, we found that TPR expression was regulated by transcriptional regulator YAP (Yes-associated protein) and TEAD1 (TEA Domain Transcription Factor 1), which act downstream nuclear effectors of the Hippo pathway. Further studies showed that supportive role of TPR in HCC was probably associated with mitochondrial function. To uncover the TPR dependent pathway in HCC process, we will go further to clarify how TPR expression is modulated by genetics and elucidate how TPR promotes hypermetabolism and high activity of proliferation. This study will provide new ideas and targets to improve the diagnosis and treatment of HCC from the way of nucleocytoplasmic transport.