PAK5调控肝癌细胞中CyclinD1的表达促进肝癌的发生发展

Hepatocellular carcinoma (HCC) is one of the greatest malignant tumor which harm to the people.The pathogenesis is not clear and bothering clinical diagnosis and treatment work. The development of HCC regulatory and control network, key gene function and clinical application value should to be further research. Our early study using of liver cancer sample genome-wide expression spectrum chip analysis and liver cancer cell line detection ,found that PAK5 in HCC on high expression. The subsequent preliminary experiments confirmed that when PAK5 was interferenced in hepatoma cell,the cell may lead to growth inhibition, G1 arrest and cell apoptosis. The preliminary studies of molecular mechanism have showed that PAK5 may be involved in the regulation of expression of cyclin D1.These results suggest that PAK5 may be an important node of HCC cell signal control network, its function is closely related hepatoma cell malignant behavior. This topic will be systemic analysis the affect of PAK5 and the malignant biological behavior,through the cell experiment, animal experiments, molecular biology experiment system.And confirm the PAK5 target genes (such as cyclin D1, etc.) and control mode.And useing a complete clinical follow-up data sample (over 200 cases)to verify,preliminary discuss the clinic application value of PAK5 as a molecular marker. This study will deepen the understanding of the pathogenesis of liver cancer, and provide a theoretical basis for research and development of new technologies of the clinical diagnosis and treatmenent.

肝癌是危害极大的恶性肿瘤之一，发病机制不清困扰着临床诊疗工作，肝癌发生发展调控网络和关键基因功能与临床应用价值亟待深入研究。本课题组前期利用肝癌样本全基因组表达谱芯片分析和肝癌细胞系检测发现PAK5在肝癌中呈现高表达，随后的预实验证实，在肝癌细胞中干扰PAK5能够导致增殖抑制、G1期阻滞以及细胞凋亡，初步的分子机制研究表明PAK5可能参与cyclin D1的表达调控。这些结果提示PAK5可能是肝癌细胞信号调控网络的重要节点，其功能与肝癌细胞恶性生物学行为密切相关。本课题将通过细胞实验、动物实验、分子生物学实验系统分析PAK5对肝癌细胞恶性生物学行为的作用，明确PAK5作用的靶基因（如cyclin D1等）和调控模式，并利用有完整随访资料的临床样本（200例以上）进行验证，初步探讨PAK5作为分子标志物的临床应用价值。本研究将加深对肝癌发病机制的认识，为研发临床诊疗新技术提供理论依据。