CBX8靶向EGR1促进肝癌浸润转移的机制研究

肝细胞癌恶性度高，预后差，已有研究表明CBX8在肿瘤发生发展中发挥重要作用，但其分子机制及在肝癌中的作用均尚未明了。我们前期观察到转录因子CBX8在肝癌中高表达，且与患者预后差相关;基因测序和预实验研究显示：①CBX8上调EGR1表达且促进肝癌细胞增殖和迁移；②CBX8表达受HBx调控；③临床肝癌样本中，CBX8与EGR1、HBx表达均呈正相关。因此，我们提出CBX8受HBx调控并靶向EGR1，促进肝癌细胞浸润转移的假说。本项目拟采用一系列免疫学及细胞生物学实验，构建细胞及动物模型，在蛋白表达及细胞功能上，明确CBX8和EGR1在肝癌中的表达及其临床意义，揭示CBX8高表达的调控机制，阐述HBx-CBX8-EGR1通路在肝癌细胞增殖及迁移中的作用及其机制，从而获得CBX8参与肝癌进展的可靠证据，为诠释肝癌发生发展的分子机制和寻找肝癌治疗新靶点提供科学依据。

Hepatocellular carcinoma (HCC) is one of the most prevalent manlignancies with high morbidity and mortality. However, the nature of HCC progression remains elusive. Previous data suggest that CBX8 plays an important role in HCC progression. In preliminary study, we found that (a) CBX8 was up-regulated and significantly associated with poor prognosis, (b) CBX8 overexpression markly up-regulated EGR1 and promote cell proliferation and migration, (c) CBX8 expression was modulated by HBx, (d) CBX8 expression was closely correlated with the expresion of EGR1 and HBx in clinical HCC samples. Based on the findings, we assume that CBX8, modulated by HBx, promotes tumor invasion and metastasis via targeting EGR1. In this study, we aim to detemine the expression of CBX8 and EGR1 and the clinical significances in HCC, to disclose the regulation of CBX8, and to reveal the mechanism via which HBx-CBX8-EGR1 promotes cell proliferation and migration in HCC. Our study is likely to provide not only solid evidence that CBX8 is involved in HCC progression, but also a potential biomarker for HCC clinical management.