HPPCn调控miR-17-92促进肝细胞癌生长转移的作用和机制研究

Hepatopoietin Cn是一个肝细胞刺激因子，已有的研究结果表明HPPCn的表达与肝癌的发生和发展密切相关，可能成为肝癌治疗的新靶点。miRNA作为一种非编码小分子单链RNA在肝癌的发生发展中发挥重要作用。前期实验结果显示HPPCn能够促进肝癌细胞中miR-17-92及其上游转录启动基因c-myc的表达。miR-17-92 基因簇是一个高度保守的基因簇，其参与调控肝癌细胞生物学特性的作用和机制还不清楚。本申请项目在以往研究的基础上，重点围绕HPPCn/c-myc/miR-17-92调控肝癌细胞生长和转移的作用和机制，通过建立细胞及基因敲除动物模型，并结合临床肝癌病人的标本观察，系统分析HPPCn/c-myc/miR-17-92信号在肝细胞癌发生及转移过程中的作用和机制。该课题将为进一步揭示肝癌发生和转移的分子机制提供新的思路，同时可能为HCC防治提供新的药物靶标分子。

HPPCn ( Hepatopoietin Cn ), a hepatic stimulator factor isolated from hepatic stimulator substance, was confirmed to be related with the development of hepatocellular carcinoma. MicroRNA is a non-coding single chain RNA, and play an important role in the occurrence and development of human hepatocellular carcinoma. The experimental results showed that HPPCn can increase the expression of miR-17-92 and c-myc in hepatoma cells. MiR-17-92 is a highly conserved gene cluster, encoding miR-17-5p, miR-17-3p, miR-18a, miR-19a, miR-20a, miR-19b-1 and miR-92-1. Their involvement and the roles in hepatocellular carcinoma is not clear. This project is focused on the roles of the HPPCn / c-myc / miR-17-92 signaling pathway in liver cancer cell growth and metastasis process through establishing cell and gene knockout animal models and analyzing clinical data from patients with hepatocellular carcinoma.