MiR-17-92-cluster促进鼻咽癌恶性进展的分子机制及基于该家族的纳米核酸药物的治疗性研究

项目名称： MiR-17-92-cluster促进鼻咽癌恶性进展的分子机制及基于该家族的纳米核酸药物的治疗性研究

项目编号： No.81502335

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： 吕晓明

作者单位： 南方医科大学

项目金额： 18万元

中文摘要： MiR-17-92 cluster家族在多种恶性肿瘤中过度表达，发挥着明显的致癌促癌的作用，被称为“头号致癌miR”。 然而在鼻咽癌的研究中，鲜有miR-17-92 cluster报道与鼻咽癌的发生发展有关。我们前期的研究结果提示miR-17-92 cluster 家族在鼻咽癌中的表达确实与鼻咽癌的恶性进展有关。据此，本项目将采用临床样本分析和体内外实验证实该miRNA家族成员对鼻咽癌恶性进程的影响,明确他们的靶基因和涉及的多个相关信号通路；进一步设计miR-17-92 cluster家族及其同源体miRNA的Antisense，运用纳米基因载体导入肿瘤细胞，抑制这些OncomiRs的表达，从而影响并减低肿瘤的恶性表征。该项目将机制研究和实验性治疗相结合，旨在进一步发现并明确miR-17-92 cluster家族及其同源体的成员在介导鼻咽癌恶性进展中的新机制，并为今后临床转化提供新的依据。

中文关键词： 鼻咽癌；miR-17-92；cluster；肿瘤恶性进展；纳米核酸药物

英文摘要： The miR-17-92 cluster is among the best-studied miRNAs in carcinogenesis, also known as ‘oncomiR-1’. To our knowledge, few lines of evidence support that miR-17-92 cluster and its paralogues may contribute to the aggressiveness of nasopharyngeal carcinoma (NPC). In our previous study, we observed that high expressions of miR-17-92 cluster and its paralogues were associated with NPC aggressiveness. Therefore, this project will firstly perform clinical sample analyses as well as in vivo and in vitro experiments to confirm the effects of miR-17-92 cluster and its paralogues on NPC aggressiveness, exploring their target genes and dependent downstream multi-signaling pathways. Furthermore, we plan to design the antisense of miR-17-92 cluster and its paralogues to inhibit the expressions of these oncomiRs, and thus slow down the malignant progress of NPC. This project will be the combination of the mechanism analysis with experimental treatment, aiming to discover the novel mechanism of miR-17-92 cluster and its paralogues -mediated malignant progression, which may be helpful for the clinical translation in the future.Importantly, in view of the anatomical features and pathological characteristics of NPC, we try to develop a new nano-oligonucleotide drug for nasopharyngeal carcinoma based on miR-17-92 Cluster, which has a good curative effect, low-cost, convenience and popularization.

英文关键词： nasopharyngeal carcinoma ;miR-17-92 cluster;tumour aggressiveness;Nano-oligonucleotide drug