miR-520c-3p对肺腺癌的抑制作用及其机制的研究

项目名称： miR-520c-3p对肺腺癌的抑制作用及其机制的研究

项目编号： No.81501984

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： 于筱舟

作者单位： 天津医科大学

项目金额： 18万元

中文摘要： microRNA对于肿瘤的发生发展具有重要作用。我们在前期工作中证明miR-520c-3p在肺腺癌中水平较低，并且具有抑制肿瘤生长、转移和代谢的作用。其中，直接调控胸腺基质淋巴生成素的肿瘤免疫机制起到了重要作用。此外，肺腺癌中AKT2作为与肿瘤生长密切相关的分子，表达水平增高，与miR-520c-3p水平呈负相关趋势，并且生物信息学软件预测该分子与miR-520c-3p具有高度结合可能性，提示除了免疫机制，AKT2可能发挥了重要作用。本研究检测并分析miR-520c-3p水平、AKT2水平、增殖、代谢和转移等指标的水平和关系。于细胞系、小鼠和患者中，验证AKT2为直接靶点，检测miR-520c-3p多方面抑制肿瘤的功能，并证实AKT2在其中发挥的关键作用。本研究深化认知miR-520c-3p在肺腺癌中的生物学功能及相关机制，为寻找新的诊断指标、治疗手段，优化相关核医学检查提供理论基础。

中文关键词： 肺肿瘤；微小RNA；蛋白激酶B；正电子发射计算机断层显像；肺腺癌

英文摘要： microRNAs play a important role in cancer development. Our previous work proved that miR-520c-3p was down-regulated in lung adenocarcinoma, which can suppress tumor growth, metastasis and metabolism. Within, a tumor immune mechanism that miR-520c-3p directly regulate thymic stromal lymphopoietin participates in this process. Also, the expression of AKT2, as an important factor in cancer development, significantly elevated in lung adenocarcinoma, which was negatively associated with the level of miR-520c-3p. Bioinformatics software also predicted that miR-520c-3p may bind to AKT2 mRNA very likely. These evidences indicated that except for cancer immune mechanism, AKT2 may also critical. This study will test the level of miR-520c-3p, AKT2, growth, metastasis and metabolism, and analyze their interaction. In cell lines, mice, and patients, a series of experiments such as the direct target of AKT2, multiple function of miR-520c-3p and critical role of AKT2 will be finished. This study will further discuss biological function of miR-520c-3p in lung adenocarcinoma and relevant mechanisms. It provided theoretical basis for searching new diagnosis target, developing new treatment method and optimizing nuclear medical examination.

英文关键词： lung cancer;microRNA;AKT;PET-CT;lung adenocarcinoma