miR-143调控MSC及通过MSC来源囊泡参与肿瘤抑制的机制研究

项目名称： miR-143调控MSC及通过MSC来源囊泡参与肿瘤抑制的机制研究

项目编号： No.31500739

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 赵晓寅

作者单位： 浙江工业大学

项目金额： 20万元

中文摘要： 间充质干细胞（MSC）具有低免疫原性、免疫调节能力以及向肿瘤部位迁移的能力。我们前期研究发现，在MSC中高表达miR-143能够抑制PGE2、IL-6、IL-8的分泌，并且高表达miR-143的MSC所分泌的囊泡也能够高表达miR-143。已知在肺癌等恶性肿瘤中过表达miR-143能够显著抑制肿瘤。此外PGE2、IL-6、IL-8在肿瘤微环境中能够起到促肿瘤作用。因此，推测miR-143可能能够通过抑制MSC促肿瘤因子的表达使其成为抑肿瘤倾向的MSC，并通过MSC来源囊泡直接抑制肿瘤。本项目将分析mir-143对MSC抗肿瘤功能的影响；揭示mir-143调控MSC及通过MSC来源囊泡发挥肿瘤抑制作用的机制；体内评估miR-143调节的MSC对肿瘤小鼠模型的治疗作用。本项目的完成将为通过MSCs治疗肿瘤提供新思路和新技术。

中文关键词： miR-143；间充质干细胞；囊泡；肿瘤抑制

英文摘要： Mesenchymal stem cells (MSC) have low immunogenicity, immunomodulatory capacity and migration ability towards tumor. In our previous studies, we found that high-expression of miR-143 in MSC can suppress the secretion of PGE2, IL-6 and IL-8, and vesicles derived from MSC with high miR-143 expression can also highly express miR-143. As well known, over-expression of miR-143 in malignancies such as lung cancer has significantly suppressive effect on tumors. Besides, PGE2, IL-6 and IL-8 can promote tumor development in tumor microenvironment. Hence, we suppose that miR-143 can convert MSC into cells with tumor-suppression tendency via regulating the expression of tumor-promoting factors in MSC, and exert direct suppressive effect on tumors via MSC-derived vesicles. Our project is to analyze the effect of miR-143 on the tumor-suppression function of MSC; to reveal the tumor-suppression mechanism of miR-143 via MSC-regulation and MSC-derived vesicles; and to perform in-vivo assessment for the therapeutical action of MSC regulated by miR-143 on tumor model mice. We will provide new sight and technology for tumor treatment using MSC.

英文关键词： microRNA-143;mesenchymal stem cells;vesicles;tumor suppression