H19/HOTS天然正反义转录本的交互竞争调控滋养细胞功能的机制研究

项目名称： H19/HOTS天然正反义转录本的交互竞争调控滋养细胞功能的机制研究

项目编号： No.81501272

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： 卢林杉

作者单位： 中国人民解放军第四军医大学

项目金额： 18万元

中文摘要： 滋养细胞以特定的时空次序增殖、分化、迁移和侵袭是保证胚胎成功着床、胎盘正常发育及妊娠顺利进行的关键。文献和我们前期研究证实，H19和H19天然反义转录本HOTS均参与滋养细胞功能调控和胎盘发育，并均可作用于IGF2；其中H19反义转录本对IGF2具有正向调控作用，与H19作用相反；而IGF2具有促进滋养细胞侵袭和胎盘生长的作用。据此我们推测，H19与其反义转录本HOTS之间存在交互拮抗作用，它们可通过竞争IGF2，参与调控滋养细胞生物学功能；H19/HOTS之间的交互调控失衡将引发滋养细胞功能异常及胎盘发育障碍，导致妊娠相关性疾病发生。本课题将开展正反义转录本H19/HOTS交互竞争，对滋养细胞生物学功能及早期胎盘发育的调控作用和分子机制研究。阐明上述问题，将有助于深入认识天然反义转录本调控理论、H19基因座分子调控机制，以及滋养细胞功能调控的分子机理，为有效防治妊娠相关性疾病探索新途径。

中文关键词： H19；非编码RNA；天然反义转录本；滋养细胞；子痫前期

英文摘要： Trophoblast specific spatial and temporal order of proliferation, differentiation, migration and invasion plays a key role in the successful implantation of embryos, the placenta normal development as well as pregnancy progression. Recent studies and our previous studies have shown that H19 and its natural antisense transcript (NAT) HOTS are involved in the regulation of trophoblast behavior and placental development, and also play an important role in IGF2 expression. The H19 antisense transcript plays a positive regulatory role of IGF2, in contrast to the H19 role. Meanwhile, IGF2 can promote the trophoblast invasion and placental growth. Based on these evidevce, we proposed that there is a reciprocal competition between H19 and HOTS. The competition could be involved in the regulation of trophoblast function and result in pregnancy associated diseases. This project will study the regulation mechanism of H19/HOTS reciprocal competition during trophoblast cells growth and early placenta development. The study will provide insights into the natural antisense transcription regulation theory, H19 gene locus regulation mechanism and provides potentially novel targets for studies of pregnancy associated diseases. 

英文关键词： H19;non-coding RNA;natural antisense transcript;trophoblast;preeclampsia