环状RNA ciRS-433下调介导心脏纤维化的分子机制研究

心脏纤维化是多种心血管疾病共同的病理改变，严重危害人类健康，目前尚缺乏有效的干预方法。环状RNA被发现广泛参与各种病理生理过程，且可以作为微小RNA（micorRNA，miRNA）的海绵体，但是它在心脏纤维化中的作用尚不清楚。项目申请人前期发现微小RNA-433（miR-433）是心脏纤维化的一个关键miRNA，论文发表在Theranostics杂志（影响因子8.854）。此次，我们初步鉴定出了一个环状RNA ciRS-433，可以作为miR-433内源性的海绵体。在此基础上，我们拟通过功能获得性和缺失性实验，在细胞水平和动物整体水平，明确ciRS-433与心脏纤维化的关系。同时，基于前期鉴定出的miR-433的2个靶基因，在细胞水平进行功能挽救实验，进一步明确ciRS-433介导心脏纤维化的分子基础。通过本课题将有望发掘出一个治疗心脏纤维化的新靶点。

Cardiac fibrosis is a common pathological change in several cardiovascular diseases, lacking effective treatments. Recently, circular RNA (circRNA) have been reported to participate in many physiological and pathological processes and can act as microRNA (miRNA，miR) sponge. However, the role of circRNA in cardiac fibrosis is still uncertain. Our previous data showed that miR-433 played a crucial role in cardiac fibrosis, which had been published in Theranostics (Impact factor:8.854). In this project, we have preliminaryly detected a circRNA as an endogenous miR-433 sponge (ciRS-433). Furthermore, we will investigate the role of ciRS-433 in cardiac fibrosis by gain-of-function and loss-of-function experiments both in vitro and in vivo. Based on two target genes of miR-433 we have proved, functional rescue experiments will be used in vitro to fully detect the downstream of ciRS-433. In this study, ciRS-433-miR-433 signaling pathway may be identified as a novel target for cardiac fibrosis.