miR-143-3p和miR-195-5p低表达在结直肠癌肝转移中的作用与调控机制研究

项目名称： miR-143-3p和miR-195-5p低表达在结直肠癌肝转移中的作用与调控机制研究

项目编号： No.81472297

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： 王守立

作者单位： 苏州大学

项目金额： 80万元

中文摘要： 在课题组前期发现miR-143-3p 和miR-195-5p的表达水平在肝转移结直肠癌（CRC）中较原位CRC中显著下降，及近期运用已建立的miRNA再表达（Oncogene,2013）和肝靶向纳米（Biomaterials, 2012）技术发现miR-143-3p 和miR-195-5p的再表达能分别通过抑制CRC细胞中靶基因蛋白（ASAPS和ITGA6）和抑制肿瘤相关巨噬细胞（TAMs）中靶基因蛋白（FGF2和MYB）抑制肿瘤细胞的侵袭和肝转移瘤的形成，提出CRC细胞和TAMs通过不同miRNA-靶基因途径协同促进CRC肝转移的新构想。本项目拟通过分子生物学、组织水平、动物体内实验和临床资料分析，进一步研究并揭示低表达miRNAs如何借助相关靶基因影响CRC肝转移进程，旨在阐明miR-143-3p和miR-195-3p低表达促进CRC肝转移的分子机制，有望为CRC肝转移防治提供新靶点

中文关键词： C08_结；直肠肿瘤；肝转移；微小RNA；机制

英文摘要： We propose this idea that CRC cells and TAMs jointly promote CRC liver metastases by a different miRNA-target gene pathway based on our previous finding that the expression level of both miR-143-3p and miR-195-5p was reduced more in liver metastatic CRC than that in primary CRC and our recent discovery that re-expression of miR-143-3p and miR-195-5p reversed the invasion ability of CRC cells and liver metastasis potential of CRC through inhibiting the expression of target gene(ASAPS and ITGA6)in CRC cells and inhibiting the expression of target gene( FGF2 and MYB)in TAMs respectively, which was derived from our newly established technology of miRNA re-expression（Oncogene,2013）and liver targeting nanotechnology（Biomaterials,2012).In this proposal, the impact of reduced expression of miRNAs on CRC liver metastasis by target gene proteins will be subjected to further analysis at molecular and tissue levels in combination with in vivo animal experimentations and clinical data analysis. These studies will yield further insight into the mechanism of how reduced expression of miR-143-3p and miR-195-3p would promote the CRC liver metastasis, leading to a new target on which more efficient methods helping prevent hepatic metastasis of CRC can be built.

英文关键词： colorectal cancer;liver metastasis;microRNA;mechanism