miR-449b调控CSFR1影响子宫内膜异位种植的分子机制

项目名称： miR-449b调控CSFR1影响子宫内膜异位种植的分子机制

项目编号： No.81471438

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： 史颖莉

作者单位： 复旦大学

项目金额： 66万元

中文摘要： 内异症是临床常见妇科疾病，病因未明而无根治手段。miR-449b是我们通过二代测序技术筛选到的一条在人内异症异位内膜、在位内膜中显著降调的miRNA。预研结果发现：抑制miR-449b表达促进内膜细胞的增殖与侵袭性，减少凋亡；生物信息学预测CSF1R是其靶基因，抑制miR-449b可上调CSF1R表达。鉴于内异症中CSF1R及其配体CSF-1高表达，并促进异位灶形成，因此提出miR-449b通过调控CSF1R影响子宫内膜异位种植的科学假说。本研究拟论证miR-449b在内异症中的生物学特征；通过过表达、沉默表达，从正反两方面论证miR-449b 对子宫内膜细胞功能影响及腹腔微环境变化影响；以CSF1R 为切入点，深入探讨miR-449b 在子宫内膜细胞异位种植过程中的分子机制；通过内异症动物模型在体评价miR-449b的功能。本研究将有助于理解内异症发病机制，有望为其防治提供新的干预靶标。

中文关键词： 子宫内膜异位症；miR-449b；CSFR1；分子机制

英文摘要： Endometriosis is a common gynecological disease with poorly understood pathogenesis. Previous research has demonstrated via microarray technique that miR-449b is significantly down-regulated both in ectopic and eutopic endometrium with endometriosis. The study also reveals knockdown of miR-449b induces endometrial cell's proliferation and invasiveness, but inhibits apoptosis. Bio-infomation suggests CSF1R is the target gene for miR-449b and down-expression of miR-449b will up-regulate CSF1R. It has known CSF1R, with its ligand CSF-1, highly expressing both in ectopic and eutopic endometrium with endometriosis,could promote the development of endometriosis. We propose miR-449b plays a significant role on endometrial ectopic implantation via the regulation of CSFR1. The research will evaluate biological property of miR-449b in endometriosis and study the influential mechanisms on endometrial cells in relation with the change of CSFR1 under the circumstances of over-expression or down-regulation of miR-449b. The influential role on CSF1R by miR-449b will also be examined by the construction of specific vectors and RNA interfering technique. The results are to be verified by using luciferase report system. Finally the function of miR-449b will be illuminated in vivo by endometriosis animal model. The innovative proposal by this study could possibly find a new target gene for the treatment of endometriosis.

英文关键词： endometriosis;miR-449b;CSFR1;molecular mechanism