LncRNA Dleu2作为ceRNA通过miR-130a-5p/SP1介导炎症反应在房颤心房重构中的分子机制

房颤严重威胁人类健康，炎症反应介导的心房重构在房颤发生中起着至关重要作用，但机制尚未阐明。我们前期利用RNA测序，发现小鼠房颤模型心房组织中LncRNA Dleu2表达升高；通过皮尔逊相关分析显示，Dleu2的异常表达与左房纤维化及炎症反应相关；功能实验显示下调Dleu2的表达可减轻心房炎症反应和纤维化并降低房颤的发生。进一步运用生物信息学结合分子生物学研究发现，miR-130a-5p可与Dleu2及SP1直接结合，且Dleu2可通过介导SP1高表达促使炎症因子TNF-α表达参与心房重构，提示Dleu2可能作为ceRNA通过miR-130a-5p/SP1介导炎症反应导致房颤心房重构。据此，本项目拟在细胞和动物模型中阐明Dleu2在房颤心房重构中的作用及分子机制，并探究Dleu2及相关通路分子在房颤发生中的病理性意义。通过本项目的实施，有望为Dleu2在房颤后续转化医学研究中奠定理论基础。

Atrial fibrillation is a common atrial arrhythmia with serious threat to human health, atrial remodeling induced by inflammatory response plays an important role in the occurrence of atrial fibrillation，however, the mechanism has not yet been clarified. In our preliminary studies, we found the expression of LncRNA Dleu2 was upregulated in the atrial tissue of mice with atrial fibrillation by RNA sequencing, and was also positively correlated with atrial fibrosis and inflammatory response by pearson analysis. Functional experiments showed that down-regulation of Dleu2 expression alleviated inflammatory response and atrial fibrosis，and reduced the incidence of atrial fibrillation. Bioinformatics analysis combined with molecular biology technology suggest that miR-130a-5p can directly bind to Dleu2 and SP1, furthermore, Dleu2 promoted atrial remodeling mediated by the inflammatory factor TNF-α which resulted by upregulating SP1. Suggesting that Dleu2 may function as ceRNA for miR-130a-5p/SP1 regulated atrial remodeling of atrial fibrillation through regulating inflammatory response. In this project, we intend to elucidate the role and molecular mechanism of Dleu2 in atrial remodeling of atrial fibrillation in cell and animal models, and explore the pathological significance of Dleu2 and related pathway molecules in the occurrence of atrial fibrillation. The present study will lay a theoretical foundation for Dleu2 in the future translational medicine research for atrial fibrillation.