Epimorphin调控的miR-107在肝癌侵袭和转移中的作用研究

项目名称： Epimorphin调控的miR-107在肝癌侵袭和转移中的作用研究

项目编号： No.81201611

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 贾雅丽

作者单位： 中国人民解放军军事医学科学院

项目金额： 23万元

中文摘要： 肝癌的侵袭和转移是导致患者治疗失败和死亡的重要原因。我们先前研究发现Epimorphin（一个肝脏内特异性表达在肝星状细胞表面的膜蛋白）能够通过激活FAK-ERK- MMP9信号通路促进肝癌细胞的侵袭和转移。为进一步了解Epimorphin促进肝癌转移的调控方式，本研究拟从表观遗传学角度对其进行深入研究。近年来，microRNAs因其在肿瘤转移中的重要作用而备受人们关注。我们初步研究结果表明：(1) 在Epimorphin作用下，肝癌细胞中的miR-107表达明显上调；(2) 外源性过表达miR-107可以显著增强肿瘤细胞的侵袭能力。在此基础上，我们提出新的假说：Epimorphin调控的miR-107能够通过靶向基因"X"促进肝癌的侵袭和转移。本项研究将在人肝癌细胞系、人肝癌细胞系裸鼠体内实验和人类肝癌临床标本三个层面深入验证我们提出的假说。

中文关键词： 表皮形态发生素；miR-107；肝细胞癌；侵袭；转移

英文摘要： Invasion and metastasis of liver cancer are very significant causes leading to treatment failure and patients' death. Hepatic stellate cells (HSC) can secrete considerable soluble factors and extracellular matrix in tumor microenvironment, which play very important roles in the process of hepatocarcinogenesis. Our previous work has shown Epimorphin, one membrane protein expressed specifically by HSC in liver, regulates liver cancer invasion and metastasis via FAK-ERK-MMP9 axis. To deeply understand the regulation of Epimorphin which can promote liver cancer metastasis, we continue to study it from a perspective of epigenetics. In recent years, microRNAs have been pain much attention for their important roles in tumor metastasis. Our initial study has indicated that Epimorphin could up-regulate miR-107 expression in liver cancer cell; what's more, exogenous overexpression of miR-107 could remarkably promote invasion of liver cancer cells. On this basis, we raise a new hypothesis: miR-107 regulated by Epimorphin can promote liver cancer invasion and metastasis through targeting gene "X". We will verify this hypothesis through human liver cancer cell lines, nude mouse intrahepatic metastasis of human liver cancer cells and human hepatoma clinical specimen.

英文关键词： Epimorphin；miR-107；HCC；invasion；metastasis