病理性心肌肥厚是导致心力衰竭的重要病理过程，探究其分子机制可为防治心力衰竭提供干预靶点。环状RNA调控心血管功能，但是其在病理性心肌肥厚中的作用多不清楚。我们的预实验发现，circ-ZNF521在病理性心肌肥厚中表达上调，且其可能通过竞争性结合miR-17-3p起效，而miR-17-3p下调可促进病理性心肌肥厚，PTEN是其靶基因。因此提出假说：circ-ZNF521通过竞争性结合miR-17-3p上调靶基因PTEN促进病理性心肌肥厚。本课题将基于病理性心肌肥厚的细胞及动物模型，首先通过功能过表达/缺失实验明确circ-ZNF521介导病理性心肌肥厚的作用，然后分别通过circ-ZNF521/miR-17-3p和circ-ZNF521/PTEN的功能逆转实验阐明circ-ZNF521介导病理性心肌肥厚的分子机制。本课题将为防治心肌肥厚及心力衰竭提供新靶点。

Pathological myocardial hypertrophy is an important pathological process leading to heart failure. Exploring its molecular mechanism can provide intervention targets for the prevention and treatment of heart failure. Circular RNAs regulate cardiovascular function, but their role in pathological myocardial hypertrophy is unclear. Our preliminary study found that circ-ZNF521 was up-regulated in pathological myocardial hypertrophy, and it might be activated by competitive binding to miR-17-3p, while inhibition of miR-17-3p could promote pathological myocardial hypertrophy via targeting PTEN. Therefore, it is hypothesized that circ-ZNF521 promotes pathological myocardial hypertrophy by competitive binding to miR-17-3p and up-regulating PTEN. Based on the cellular and animal models of pathological myocardial hypertrophy, we will first clarify the role of circ-ZNF521 in the pathogenesis of pathological myocardial hypertrophy through function overexpression/deletion experiments. Then we will elucidate the molecular mechanism of circ-ZNF521 mediating pathological myocardial hypertrophy through the functional reversal experiments of circ-ZNF521/miR-17-3p and circ-ZNF521/PTEN, respectively. This project will provide a new target for the prevention and treatment of myocardial hypertrophy and heart failure.