BMPR2 mRNA作为内源竞争性RNA在先天性心脏病相关肺动脉高压中对NOTCH1表达的调控机制研究

Pulmonary arterial hypertension frequently arises in patients with congenital heart disease, leading to inoperability and significant increased mortality. It has become a much more important medical and social issue as more patients with structural heart disease survive into adulthood. Evidence has emerged that miRNAs play a key role in regulating the cellular processes involved in pulmonary vascular remodeling. Although we have published our speculation with theoretical evidence that competing endogenous RNA network also play pivotally, the role of competing endogenous RNAs in the pathogenesis of pulmonary arterial hypertension has not been well studied. Hence, according to our previous work in human lung specimens, we hypothesize that BMPR2 mRNA may regulate NOTCH1 as competing endogenous RNA via competing for microRNA-27b binding in the pathogenesis of pulmonary hypertension related to congenital heart defect. In this 2 years’ project, we will verify the role of BMPR2 mRNA regulating NOTCH1 as competing endogenous RNA via competing for microRNA-27b binding in human pulmonary arterial endothelial cells.

先天性心脏病（CHD）是我国首位出生缺陷疾病，继发性肺动脉高压(PAH)是影响其预后的主要因素。我们前期发现microRNA参与调控CHD-PAH的进展；同时研究已证实BMPR2的突变可能是CHD患儿出现严重PAH的危险因素。本研究拟在人肺动脉内皮细胞（中，首先验证BMPR2 mRNA是microRNA-27b的靶位点；进一步通过低表达、高表达BMPR2 mRNA，观察NOTCH1 mRNA及蛋白表达的水平，并进一步在之前获得的CHD-PAH患儿肺组织标本中验证；最后在Dicer突变细胞中，验证BMPR2 mRNA的调节作用是由microRNA介导的，从而证明BMPR2 mRNA作为ceRNA，通过调节microRNA-27b与NOTCH1相互作用影响CHD-PAH的发生。本研究将为CHD-PAH相关表观遗传研究提供新的视野，证实BMPR2作为CHD-PAH新的干预位点的可能。