环状RNA hsa_circ_0099734调控miR-499-5p/KCNN3-IK,Ca在房颤中作用和机制的分子流行病学研究

目前房颤的治疗存在一定局限性，亟需从新的角度研究房颤发病机制，探索新的治疗靶点和生物标志物。环状RNA在多种心血管疾病中起到重要作用，但在房颤发生中的作用和机制还罕有研究，本课题组利用全转录组测序及qRT-PCR验证，发现环状RNA hsa_circ_0099734在房颤患者心房组织中的表达显著高于对照组。根据生物信息学分析、系列预实验和已有的研究证据，我们提出：hsa_circ_0099734可能作为miR-499-5p的内源性分子海绵，竞争性吸附miR-499-5p，通过解除miR-499-5p对KCNN3表达的抑制，上调KCNN3表达从而调控IK,Ca电流密度以及APD，影响房颤发生发展。本项目拟从人群、细胞和分子不同水平，研究hsa_circ_0099734在房颤发生发展中的作用和机制，为深入认识房颤的分子基础，探索房颤潜在的治疗新靶点及生物标志物提供新的理论依据。

The current treatment methods for atrial fibrillation (AF) have some limitations. Thus, identification of new effective therapeutic targets may provide alternative strategies to relieve the burden of AF and find novel biomarkers. Recent studies suggest critical roles of circular RNA (circRNA) in modulating the initiation and progression of cardiovascular diseases. But to the best of our knowledge, the role of circRNA in AF has rarely been investigated. We found the expression level of hsa_circ_0099734 was significantly higher in the atrial tissue of AF patients than in controls by RNA sequencing and qRT-PCR validation. According to bioinformatics analysis, a series of pilot studies and previous evidences, we proposed the hypothesis that hsa_circ_0099734 may function as a sponge for miR-499-5p and regulate the expression of KCNN3,IK,Ca and APD, and then play critical role in modulating the initiation and progression of AF. We plan to explore the role and mechanism of circular RNA hsa_circ_0099734 in the initiation and progression of AF. This project will provide a basis for further understanding of the aetiology underlying. It is of great significance to find new therapeutic targets and biomarkers.