LncRNA-HOTAIR作为ceRNA调控FZD7表达在骨关节炎中的作用及机制研究

项目名称： LncRNA-HOTAIR作为ceRNA调控FZD7表达在骨关节炎中的作用及机制研究

项目编号： No.81501919

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： 邢丹

作者单位： 天津市天津医院

项目金额： 18万元

中文摘要： 骨关节炎(OA)是危害人类健康的骨关节病，其发生发展机制尚未完全清楚。我们前期工作表明长链非编码RNA（LncRNA)HOTAIR参与软骨细胞退变，HOTAIR过表达促进FZD7表达。基因序列分析证实HOTAIR靶基因包括miR-1。研究进一步证实，抑制miR-1将促进其靶基因FZD7表达从而激活Wnt/β-catenin信号通路，最终导致软骨细胞退变。据此我们推测HOTAIR可能作为竞争性内源RNA(ceRNA)抑制miR-1与靶mRNA结合而上调其表达。在本研究中，将利用siRNA、质粒转染、荧光素酶实验、RNA结合蛋白免疫沉淀及生物信息学等技术，以软骨细胞为对象，由HOTAIR与miR-1参与软骨细胞退变的现象出发，从ceRNA调控FZD7表达角度探讨HOTAIR在OA中作用及机制，为OA防治提供新靶点与新策略，有助于深入理解非编码RNA与mRNA之间网络调控在OA发生发展中的作用。

中文关键词： 长链非编码RNA；骨关节炎；竞争性内源性RNA；微小RNA；卷曲蛋白7

英文摘要： Osteoarthritis (OA) is bone and joint disease harmful to human health, and its progression mechanisms are not yet fully understood. The preliminary work indicates that the long non-coding RNA (LncRNA) HOTAIR is involved in chondrocyte degeneration, HOTAIR overexpression promotes FZD7 expression. Gene sequence analysis has confirmed that HOTAIR target genes include miR-1. The study further demonstrates that inhibition of miR-1 will contribute to the expression of its target genes FZD7 and activate Wnt/β-catenin signaling pathway, leading to the degeneration of cartilage cells. Accordingly, we speculate HOTAIR may serve as a competitive endogenesis RNA (ceRNA) to inhibit the bonding of miR-1 and target mRNA and upregulate its expression. In this study, we will use siRNA, plasmid transfection, luciferase assay, RNA-binding protein immunoprecipitation and bioinformatics technology, taking chondrocytes as the object, starting from the phenomenon of HOTAIR and miR-1 are involved in the degeneration of chondrocyte, from the perspective thatceRNAregulates and controls FZD7 expression, to explore the effect and mechanism of HOTAIR in OA, providing new targets and new strategies for prevention and treatment of OA, which helps us to understand the role of the network regulation between non-coding RNA and mRNA in occurrence and development of OA.

英文关键词： Long non-coding RNA;Osteoarthritis;Competing endogenous RNA;MicroRNA;FZD7