中文摘要
心血管疾病是人类生命的头号杀手,因此阐明心脏疾病的致病机理是目前生命科学和医学界的重要课题。越来越多的非编码小RNA(miRNA)被发现参与包括心肌肥大在内的多种心脏疾病的发生。然而miRNA之间是否相互作用,以及这种相互作用是否影响心肌肥大的发生尚未见报导。我们前期研究发现miR-223对心肌肥大有促进作用,而且能够下调具有抑制心肌肥大功能的miR-541和miR-133a的表达。在此我们将研究miR-223和miR541、miR-133a之间的相互作用对心肌肥大的影响,并探索下游靶标,从细胞水平和动物水平研究它们在心肌肥大过程中的功能。验证通过miRNA-miRNA相互作用影响心肌肥大的新机制。通过算法优化,全面预测与心肌肥大相关的miRNA之间的调控网络,并通过实验检验miRNA调控网络的实际作用,为心肌肥大的诊断和治疗提供新的理论依据。
英文摘要
Cardiovascular diseases are the leading cause of human death globally. The elucidation of regulation factors of cardiovascular diseases is of the major scientific and therapeutic importance. Recently the pathological function of miRNAs in cardiac hypertrophy has been extensively explored. However, whether miRNA interact with other miRNAs and the potential function of the interaction in cardiac hypertrophy remain unknown. We have discovered that miR-223 stimulates hypertrophy occur, and more importantly, it can impair the expression of hypertrophy suppressors miR-541 and miR-133a. Here by study the role of interaction between miR-223 and miR-541/miR-133a, we will first time uncover that miRNA-miRNA interaction regulates cardiac hypertrophy. In addition, we will improve the sequence analyze strategy together with laboratory research to predict and characterize the entire miRNA-miRNA interaction network in cardiac hypertrophy. This will provide novel direction for cardiac hypertrophy diagnosis and treatment.
