长链非编码RNA- - MIR17HG靶向TGFβ/BMP信号通路调控腭发育的分子机制

项目名称： 长链非编码RNA- - MIR17HG靶向TGFβ/BMP信号通路调控腭发育的分子机制

项目编号： No.81200771

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 李灵

作者单位： 四川大学

项目金额： 23万元

中文摘要： 先天性腭裂是严重影响患儿身心健康的多基因遗传疾病，其致病基因还不明确。腭间充质细胞的正常增殖、胞外基质分泌和成骨细胞向分化是正常腭发育的保证。研究表明CMYC可促进长链非编码RNA- - MIR17HG的转录；MIR17HG的剪切产物可通过靶向作用于SMAD依赖的TGFB通路成员；SMAD依赖的TGFB/BMP通路成员可调控腭间充质细胞增殖、凋亡、胞外基质分泌和成骨细胞向分化。本项目拟构建MIR17HG基因高表达和沉默的小鼠腭间充质细胞，以此为模型，分析MIR17HG通过哪些剪切产物靶向调控TGFB/BMP信号通路中哪些成员从而影响腭间充质细胞增殖、凋亡、胞外基质分泌和成骨向分化等功能，并探索MIR17HG转录调控机制，最终阐明"CMYC→MIR17HG→TGFB/BMP SMADs→SMAD靶蛋白"这一关键调控通路在腭间充质细胞中的存在。

中文关键词： 长链非编码RNA；MIR17HG；miRNA；腭间充质；发育

英文摘要： Cleft palate is a multi-factorial congenital malformation, whose genetic causes is unclear. The normal proliferation,extracellular matrix(ECM) secretion and osteogenesis of palatal mesenchymal cells(PMCs) play important roles during palatal development. Recent studies show that CMYC promote transcription of long noncoding RNA-MIR17HG; the splicing production of MIR17HG target components of SMAD dependent TGFB signaling pathway；SMAD dependent TGFB/BMP pathway regulate proliferation, apoptosis, ECM secretion and osteogenesis of PMCs. Here，we want to construct PMCs with increased/decreased expression of MIR17HG,and show that how could CMYC regulate transcription of MIR17HG, which splicing products of MIR17HG would target SMAD dependent TGFB/BMP pathway to regulate proliferation, apoptosis, ECM secretion and osteogenesis of PMCs. We'll finally indicate that whether "CMYC→MIR17HG→TGFB/BMP SMADs→SMAD target genes"pathway exists in PMCs during palatal development.

英文关键词： LncRNA；MIR17HG；miRNA；palate mesenchymal cells；development