特异靶向肿瘤早期预测因子：长链非编码RNA MALAT1正电子分子探针的研发及实验研究

项目名称： 特异靶向肿瘤早期预测因子：长链非编码RNA MALAT1正电子分子探针的研发及实验研究

项目编号： No.81471704

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 董孟杰

作者单位： 浙江大学

项目金额： 70万元

中文摘要： 肿瘤治疗的失败关键在于预后不良，如能研发高灵敏、高特异肿瘤早期预测肿瘤预后的正电子分子探针无疑对于肿瘤的早期防治、改善预后意义非凡。长链非编码RNA为目前肿瘤研究中全新热点，对肿瘤发生发展的认识带来革命性变化，MALAT1基因是与肿瘤恶性表型相关的长链非编码RNA，已证实其具有在肿瘤中异常高表达，与肿瘤侵袭转移、预后密切相关，尤其已成为肿瘤复发预测因子及预测疾病预后不良的重要指标。本课题拟在先期研究：MALAT1表达与肝癌预后转移复发，癌细胞增殖、迁移和侵袭力等恶性生物学行为密切相关；MALAT1过表达是预测肝癌术后复发的独立预后因子；MALAT1 ASO不仅特异靶向 MALAT1，而且具有时间、浓度依赖性等具备了正电子分子探针研发要素基础上，深入研发特异靶向MALAT1 的正电子小分子探针；并利用小动物PET技术筛选生物活性更优佳的特异分子探针。研发的正电子小分子探针将具有自主知识产权。

中文关键词： 分子探针；长链非编码RNA；MALAT1；预测因子；小动物PET；正电子发射计算机断层成像

英文摘要： The key reason of unsuccessful tumor therapy is its poor prognosis. It will be great significance in the early diagnosis, early prevention and cure of tumor recurrence if highly-selective, highly-specific positron emission tomography(PET) molecular probe, which target to tumor prognostic factor, can be developed. Long noncoding RNA (lncRNA) is a brand-new research focus, which has brought revolutionary change for the tumorigenesis and deveolpment. MALAT1 gene is related to tumor phenotype, highly expresses in the tumor issues and is closely related to the invasion, metastasis and prognosis of tumor. MALAT1 gene has been a prognostic factor and an important sign of poor prognosis. The study will based on our previous study: the expression of MALAT1 is closely related to the metastasis, proliferation and invasion of hepatic carcinoma; MALAT1 is a solo prognostic factor to predict hepatic carcinoma occurrence; MALAT1 antisense oligonucleotides (ASO) can combine the MALAT1 specifically, and is of time and concentration dependence, which possess the essential factor to develope PET probe. Further study is to develop the PET molecular probes which can specifically target to MALAT1, and screen out the specific molecular probes being of higher biologic activity. The developed PET molecular probes will have autonomic intellectual property.

英文关键词： Molecular probe;lncRNA MALAT1;Predictor;Micro PET;Positron emission tomography