广西肝癌的发病率和死亡率明显高于全国水平，其发生涉及多种基因的异常表达，但分子机制尚不明确。我们前期发现转录因子DEC1与E盒的非专一性结合使其可调控多种靶基因参与肿瘤发生，生物信息学预测VIPR1与DEC1有互作关系，提示VIPR1可能在肿瘤发生中起作用。基因芯片数据和定量PCR分析揭示VIPR1在肝癌中低表达，且此现象可被DNA甲基化转移酶抑制剂和组蛋白去乙酰化酶抑制剂逆转，提示DNA甲基化和组蛋白乙酰化可能是调控VIPR1表达的主要方式。GO分析表明VIPR1可能通过调控MAPK信号通路影响肝癌发生。本项目拟在组织、细胞系和裸鼠中研究DNA甲基化和组蛋白乙酰化与肝癌的相关性以及对VIPR1表达的调控作用，观察启动子甲基化对细胞生物学行为的影响，分析验证VIPR1对MAPK信号通路的调控模式。本研究不仅有助于阐明VIPR1影响肝癌发生的分子机理，而且能为肝癌的防治提供新线索。

The morbidity and mortality of liver cancer in Guangxi province are significantly higher than the national level. Its occurrence and development are related to the abnormal expression of various genes, but its exact pathogenesis still remains unclear. Our previous research revealed that the DEC1 function as transcription factors by non-specific binding to E-box region in the proximal promoter of target genes allowed it to regulate a number of potential target genes and play important roles in pathological processes such as cancer. Bioinformatics method predicted the interactions between VIPR1 and DEC1. These results indicated that VIPR1 might play a role in tumorigenesis. Gene-chip data and quantitative PCR analysis displayed a low expression level of VIPR1 in hepatocellular carcinoma (HCC). DNA methyltransferase inhibitor and histone deacetylase inhibitor could upregulate significantly the expression level of VIPR1 in human HCC cell line. These results suggested that epigenetic regulation，such as DNA methylation and histone acetylation, was the main way of VIPR1 silencing. GO analysis revealed that VIPR1 might play a role in the occurrence of HCC by regulating the MAPK signal pathway. This project aims to investigate the correlation between HCC and the date of DNA methylation and histone acetylation and the regulation of DNA methylation and histone acetylation on VIPR1 expression level by using HCC tissues, cell lines and nude mice. Furthermore, we aim to study the effect of promoter methylation on cell biological behavior and the role of VIPR1 in the regulation of MAPK signaling pathway. This study helps to elucidate the role of VIPR1 in the pathogenesis of liver cancer and provides new clues for the prevention of HCC.