TINCR通过与miR-31和C/EBP-α相互作用调控脂肪基质干细胞成脂分化的机制研究

项目名称： TINCR通过与miR-31和C/EBP-α相互作用调控脂肪基质干细胞成脂分化的机制研究

项目编号： No.81500832

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： 陈林

作者单位： 中南大学

项目金额： 18万元

中文摘要： 近年发现miRNAs和lncRNAs两类非编码RNA在干细胞的分化中发挥重要作用，而它们在干细胞成脂分化过程中的相互作用和网络调控机制并不清楚。我们前期研究发现一个在脂肪基质干细胞成脂分化后上调的lncRNA TINCR和一个下调的miRNA miR-31。外源性过表达miR-31后，在成脂分化受抑制的同时，TINCR连同成脂分化关键转录因子C/EBP-α一并下调。借助生物信息学平台，我们发现TINCR、miR-31和C/EBP-α之间相互具有潜在作用位点，结合实验结果，推测三者可能相互作用并参与成脂分化的调控。因此，本项目拟深入研究三者之间的关系及其调控脂肪基质干细胞成脂分化的分子机制。本项目的完成将为更深入了解成脂分化过程中非编码RNAs的功能奠定理论及实验基础，并为优化脂肪基质干细胞成脂分化诱导技术，最终实现脂肪组织工程的临床化和产业化提供理论和实验依据。

中文关键词： 脂肪基质干细胞；成脂分化；长链非编码RNA；微小RNA；脂肪组织工程

英文摘要： Recent studies have found that miRNAs and lncRNAs are two kinds of non-coding RNAs that play an important role on the differentiation process of stem cells, whereas their relationship and the molecular regulatory network in adipogenic differentiation of adipose derived stromal/stem cells (ASCs) are not clear. Our previous studies have found that a miRNA miR-31 decreased significantly and a lncRNA TINCR increased significantly during the adipogenic differentiation process of ASCs. Further studies found that exogenous overexpression of miR-31 in ASCs inhibited adipogenesis. TINCR, meanwhile, together with the crucial transcription factor C/EBP-α of adipogenesis, decreased remarkably. By bioinformatic approaches, we found that there was a binding site for C/EBP-α in the promoter region of TINCR gene and a target site for miR-31 in the 3'UTR of C/EBP-α. Furthermore, there were complementary sequences for miR-31 in the TINCR sequences. Taken together, it suggests that they may interrelate with each other. Therefore, in this project, we intend to clarify the relationship between TINCR, miR-31 and C/EBP-α, and their regulatory mechanisms in adipogenesis. The results of this project will not only provide a better understanding of the role for non-coding RNAs in adipogenesis, but also provide novel theoretical and experimental evidence for optimizing the inducement conditions for seeding cell in adipose tissue engineering.

英文关键词： adipose derived stromal/stem cells;adipogenic differentiation;long non-coding RNA;microRNA;adipose tissue engineering