组蛋白H3K9甲基化调控者miR-29家族在非小细胞肺癌发生发展中的作用及分子机制的研究

项目名称： 组蛋白H3K9甲基化调控者miR-29家族在非小细胞肺癌发生发展中的作用及分子机制的研究

项目编号： No.81502427

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 陈碧峰

作者单位： 武汉理工大学

项目金额： 18万元

中文摘要： 肺癌是一种高致死率的恶性肿瘤，对人类的经济生活造成极大的危害，但其发生的具体机制尚未完全阐述。作为肺癌的主要组织类型，非小细胞肺癌(Non-Small Cell Lung Cancer, NSCLC）因其确诊晚及预后差等特点尤其受到关注。近十年来表观遗传学研究的快速发展为研究肺癌的发生发展以及开发肺癌个性化治疗方案提供了新思路。前期研究报道miR-29（miR-29a， -29b和-29c）在NSCLC中是低表达的，但其生物学功能仍未完全阐明。本课题发现组蛋白H3K9甲基化调控者SETDB1和Suv39h1是miR-29下游共同的靶基因，暗示miR-29有可能作为H3K9甲基化的调控者参与NSCLC的发生发展。同时通过实验验证NSCLC中miR-29/SETDB1/C-MYC和miR-29/SETDB1/TP53这两个反馈调控通路，以期解释miR-29在NSCLC中低表达的潜在机制。

中文关键词： 非小细胞肺癌；miR-29；H3K9甲基化；反馈调控环路

英文摘要： Lung cancer is a malignant tumor with high fatality rate, and causes great harm to human economic life. However, the mechanisms underlying the development of lung cancer reminds largely unknown. As the major histological class of lung cancer, NSCLC has always been diagnosed at a late stage, and the patients have poor prognosis after operation. With the rapid development of epigenetics study in the last decade, the understanding of the pathogenesis of lung cancer and the development of personalized lung cancer treatment are picking up pace. Previews studies showed that miR-29 (miR-29a，-29b and -29c) were downregulated in NSCLC, but their biological roles in lung cancer development reminds largely unknown were not fully elucidate. This research found that the H3K9 methyltransferases SETDB1 and Suv39h1 were the downstream target of miR-29, indicating that miR-29 might act as a regulator of H3K9 methylation in the development of NSCLC. Meanwhile, this research proposed to verify the two feedback loops of miR-29/SETDB1/C-MYC and miR-29/SETDB1/TP53 in NSCLC, so as to partially explain the underlying mechanism of miR-29 low expression in NSCLC.

英文关键词： Non-Small Cell Lung Cancer(NSCLC);miR-29;H3K9 methylation;feedback loop